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Stanislao Morgera

Publications and source records attributed to Stanislao Morgera.

28 records · Page 2Linked to original sources
PubMed2003

Intermittent high permeability hemofiltration in septic patients with acute renal failure.

OBJECTIVE: High permeability hemofiltration (HP-HF) is a new renal replacement modality designed to facilitate the elimination of cytokines in sepsis. Clinical safety data on this new procedure is still lacking. This study investigates the effects of HP-HF on the protein and coagulation status as well as on cardiovascular hemodynamics in patients with septic shock. In addition, the clearance capacity for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) is analyzed. DESIGN: Prospective, single-center pilot trial. SETTING: University hospital. PATIENTS: Sixteen patients with multiple organ failure (MOF) induced by septic shock were studied. INTERVENTION: Patients were treated by intermittent high permeability hemofiltration (iHP-HF; nominal cut-off point: 60 kilodaltons). Intermittent HP-HF was performed over 5 days for 12 h per day and alternated with conventional hemofiltration. MEASUREMENTS AND RESULTS: Intermittent HP-HF proved to be a safe hemofiltration modality in regard to cardiovascular hemodynamics and its impact on the coagulation status. However, transmembrane protein loss occurred and cumulative 12-h protein loss was 7.60 g (IQR: 6.2-12.0). The filtration capacity for IL-6 was exceptionally high. The IL-6 sieving coefficient approximated 1 throughout the study period. The total plasma IL-6 burden, estimated by area under curve analysis, declined over time ( p<0.001 vs baseline). The TNF-alpha elimination capacity was poor. CONCLUSIONS: High permeability hemofiltration is a new approach in the adjuvant therapy of sepsis that facilitates the elimination of cytokines. HP-HF alternating with conventional hemofiltration is well tolerated. Further studies are needed to analyze whether HP-HF is able to mitigate the course of sepsis.

Acute Kidney Injury↗
PubMed2003

Combined ETA/ETB receptor blockade of human peritoneal mesothelial cells inhibits collagen I RNA synthesis.

BACKGROUND: Peritoneal fibrosis is a serious complication of peritoneal dialysis; however, the mechanisms are poorly understood. We studied osmolarity and physical stress-induced effects on collagen I RNA synthesis in human peritoneal mesothelial cells (HPMCs) and focused on endothelin as a possible mediator. METHODS: HPMCs were grown in a medium containing either d-glucose or glycerol to analyze the impact of osmolarity on mesothelial endothelin-1 (ET-1) release and on collagen I RNA synthesis [reverse transcription-polymerase chain reaction (RT-PCR)]. A cellular model of nonlaminar fluid shear stress and cellular stretch was used to analyze the effects of physical forces. To neutralize the endothelin effects, a combined ETA/ETB receptor antagonist (LU 302 872) was chosen. RESULTS: Glucose, but not glycerol, increased mesothelial ET-1 release in a concentration and time-dependent manner (P < 0.05 vs. controls). Collagen I RNA synthesis was significantly higher in glucose-challenged cell cultures (P < 0.05 vs. controls). The glucose-mediated collagen I RNA synthesis was completely inhibited by adding the combined ETA/ETB receptor antagonist to the medium. Fluid shear stress, but not cellular stretch, led to a significant increase in the mesothelial ET-1 release (P < 0.005 vs. controls) and collagen I RNA synthesis (P < 0.05 vs. controls). LU 302 872 completely inhibited these effects. CONCLUSION: We found that glucose and fluid shear stress are potent stimuli for ET-1 release and collagen I RNA synthesis in a model cellular system. Although our system is highly artificial, our findings raise the hypothesis that similar effects may occur in the peritoneal membranes of peritoneal dialysis patients and suggest that endothelin might be involved.

Cells, Cultured↗
PubMed2003

TNF-alpha elimination with high cut-off haemofilters: a feasible clinical modality for septic patients?

BACKGROUND: Renal replacement therapies with high cut-off haemofilters are new approaches in the adjuvant therapy of sepsis. We analysed the cytokine elimination capacity of a newly developed polyflux high cut-off haemofilter. Different renal replacement therapies are compared and tested for their clinical feasibility. METHODS: Blood from healthy volunteers (n=15) was incubated for 4 h with 1 mg of endotoxin and then circulated through a closed extracorporeal circuit. A newly developed polyflux haemofilter (P2SX) was used. Haemofiltration, haemodialysis and albumin dialysis were tested. IL-1ra (17 kDa), interleukin-6 (IL-6) (28 kDa), tumour necrosis factor alpha (TNF-alpha) (51 kDa), albumin (64 kDa), creatinkinase (CK) (80 kDa) and IgG (140 kDa) were measured in blood and filtrates prior to the initiation and after 5 min, 1, 2 and 4 h. RESULTS: Haemofiltration was superior to haemodialysis in the clearance capacity of all substances when applied in the 1 l/h ultrafiltration mode. Increasing the ultrafiltration rate/dialysate flow from 1 to 3 l/h led to a significant increase in cytokine clearances (P<0.001). At 3 l/h the differences between haemofiltration and haemodialysis vanished and both techniques achieved comparable cytokine clearances. Median clearance values ranged between 25 and 54 ml/min for interleukin-1 receptor antagonist (IL-1ra), 23 and 42 ml/min for IL-6 and 15 and 28 ml/min for TNF-alpha. Albumin loss was highest in the haemofiltration group with albumin clearances ranging between 7 and 13 ml/min. Using diffusion instead of convection significantly reduced the loss of albumin (P<0.01 for 1 l/h, P<0.05 for 3 l/h). Albumin dialysis was able to completely inhibit albumin loss but cytokine clearance capacity was limited. CONCLUSIONS: High cut-off haemofilters achieve high clearances for inflammatory IL-6 and TNF-alpha. Due to the high protein loss in haemofiltration, dialysis in combination with balanced protein substitution seems to be a suitable approach for clinical trials.

Acute Kidney Injury↗
PubMed2003

High permeability haemofiltration improves peripheral blood mononuclear cell proliferation in septic patients with acute renal failure.

BACKGROUND: Continuous veno-venous haemofiltration (HF) with high permeability (HP) haemofilters is a novel approach in the adjuvant therapy of septic patients. HP haemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether HP-HF has an impact on peripheral blood mononuclear cell (PBMC) proliferation and whether ultrafiltrate can alter PBMC function in isolates from healthy volunteers. METHODS: Twenty-eight septic patients with acute renal failure were randomly allocated to either HP-HF or conventional HF (C-HF). HP-HF was performed with a newly developed high-flux polyamide membrane (P2SH) with a nominal cut-off point of 60 kDa. For C-HF, a high-flux polyamide haemofilter (Polyflux 11S; cut-off, 30 kDa) was used. RESULTS: Septic patients demonstrated a significantly reduced proliferation of anti-CD3-stimulated PBMCs compared to healthy controls (P = 0.016). Initiating HF led to a restoration of the PBMC proliferation in HP-HF but not in C-HF. Exposing PBMCs isolated from healthy donors to ultrafiltrates from patients with sepsis demonstrated a significant suppressive effect of HP ultrafiltrates on the anti-CD3-stimulated PBMC proliferation (P = 0.011). Ultrafiltrate from patients with sepsis who received C-HF had no impact on PBMC proliferation. CONCLUSION: HP-HF restores PBMC proliferation in septic patients probably by eliminating immunomodulatory mediators. HP-HF may represent a new renal replacement therapy able to modulate PBMC function in sepsis.

Acute Kidney Injury↗
PubMed2003

Intermittent high-permeability hemofiltration modulates inflammatory response in septic patients with multiorgan failure.

BACKGROUND/AIM: Continuous venovenous hemofiltration with high-permeability hemofilters is a novel approach in the adjuvant therapy of septic patients. High-permeability hemofilters are characterized by an increased pore size which facilitates the filtration of inflammatory mediators. The present study examines whether intermittent high-permeability hemofiltration has an immunomodulatory effect on polymorphonuclear leukocytes and mononuclear cells. METHODS: Twenty-eight septic patients with acute renal failure were randomly allocated to either receive intermittent high-permeability or conventional hemofiltration. Intermittent high-permeability hemofiltration consisted of a daily 12-hour course of high-permeability hemofiltration alternated by conventional hemofiltration. For high-permeability hemofiltration, a newly developed high-flux polyamide membrane (P2SH) with a nominal cutoff point of 60 kD was used. For conventional hemofiltration a high-flux polyamide hemofilter (Polyflux 11S, cutoff point 30 kD) was used. RESULTS: The polymorphonuclear leukocyte phagocytosis activity before starting hemofiltration was almost double the rate of healthy controls in both groups (p < 0.001). The phagocytosis rate decreased significantly during the course of intermittent high-permeability hemofiltration (p < 0.05), whereas the values remained unchanged in the conventional hemofiltration group. Incubation of high-permeability filtrates with blood from healthy donors resulted in a significant induction of phagocytosis (p < 0.001), whereas conventional filtrates had no phagocytosis-stimulating effects. In addition, incubation of healthy-donor mononuclear cells with high-permeability but not conventional filtrates resulted in a significant tumor necrosis factor alpha release (p < 0.001). CONCLUSIONS: Intermittent high-permeability hemofiltration is a novel extracorporeal elimination modality which exhibits immunomodulatory effects on leukocytes, attenuating polymorphonuclear neutrophil phagocytosis. Further studies are necessary to elucidate whether these effects translate in a clinical improvement in patients suffering from sepsis.

Acute Kidney Injury↗
PubMed2002

Long-term outcomes in acute renal failure patients treated with continuous renal replacement therapies.

BACKGROUND: Limited health care budgets have raised the issue of how much therapy should be dedicated to critically ill patients with multiorgan and acute renal failure (ARF). No data are available on patients with ARF after hospital discharge. METHODS: We assessed long-term survival and quality of life after discharge. Nine hundred seventy-nine patients with ARF who needed continuous renal replacement therapies were analyzed retrospectively. Contact was achieved by questionnaires assessing health status and mental and physical well-being. RESULTS: The in-hospital mortality rate was 69% (n = 678). Postdischarge information was obtained from 89% (n = 267). Kaplan-Meier analyses showed surprisingly good postdischarge survival. Discharged patients had a 77% probability to survive the first 6 months. Those who did so had a probability of 89% to survive the following 6 months. After 5 years, the survival probability was 50%. Age and more than one comorbidity before hospitalization were associated with significantly lower postdischarge survival. Seventy-seven percent of questionnaire responders assessed their current health status as good to excellent, 57% were self-sustaining, and 49% stated that their quality of life had improved. Renal insufficiency remained in 41%, whereas 10% required chronic dialysis therapy. CONCLUSION: ARF is associated with a high in-hospital mortality rate. Nevertheless, patients leaving the hospital had a reasonable survival rate and good quality of life. We conclude that aggressive intensive care unit treatment is justified in these patients.

APACHE↗
PubMed2002

Low-dose prostacyclin preserves renal function in high-risk patients after coronary bypass surgery.

OBJECTIVE: Renal failure after bypass is still a threatening problem prolonging hospital care and reducing overall survival. The following pilot study was aimed to analyze whether perioperative low-dose prostacyclin infusion is able to preserve renal function in a selected group of patients who according to a poor cardiac function were stratified as high risk for the development of renal failure after bypass. DESIGN: Prospective randomized study. SETTING: Tertiary care university medical center. PATIENTS: Thirty-four patients scheduled for primary cardiac bypass surgery were included in the study (prostacyclin n = 17, control n = 17). Inclusion criteria were normal renal function before surgery and a cardiac ejection fraction <40%. INTERVENTIONS: Low-dose prostacyclin (2 ng/kg/min) was added to the standard anesthetic protocol. Infusion was started immediately before surgery and was continued for a maximum of 48 MEASUREMENTS AND MAIN RESULTS: Significant differences in the endogenous creatinine clearance were found between the prostacyclin and the control group. Whereas there was a significant drop in the creatinine clearance at 6 hrs after surgery in the control group with a prolonged recovery period, values in the prostacyclin group remained stable. Creatinine clearance before intervention was 100 +/- 22 mL/min in the control group and 91 +/- 22 mL/min in the prostacyclin group, values at 24 hr were 68 +/- 34 mL/min vs. 103 +/- 37 mL/min, respectively (p < .01). Significant findings in favor for the prostacyclin group were also found for urine output and the fractional excretion rate of sodium. CONCLUSION: This first pilot study indicates that low-dose prostacyclin may be of substantial value for preserving renal function in high-risk patients after coronary bypass surgery.

Coronary Artery Bypass↗
PubMedDate not supplied

Cytokine dialysis: an ex vivo study.

To test the hypothesis that dialysis using a new large pore membrane would achieve effective cytokine removal, blood from six volunteers was incubated with endotoxin (1 mg) and then circulated through a closed circuit with a polyamide membrane (nominal cut-off: 100 kDa). Hemodialysis was conducted at 1 or 9 L/hr of dialysate flow at the start of circulation and after 2 and 4 hours. The peak dialysate/plasma concentration ratios were 0.92 for interleukin (IL)-1beta, 0.67 for IL-6, 0.94 for IL-8, 0.33 for tumor necrosis factor (TNF)-a, and 0.11 for albumin. The dialysate/plasma ratios for all cytokines and albumin were decreased with increased dialysate flow from 1 to 9 L/hr (p < 0.05). Clearances for IL-1beta, IL-6, and IL-8, however, were significantly improved with increased dialysate flow (p < 0.01). There was no increase in TNF-a clearance (not significant) and a decrease in albumin clearance (p < 0.01). The peak clearance at 9 L/hr was 33 ml/min for IL-1beta, 19 for IL-6, 51 for IL-8, 11 for TNF-alpha, and 1.2 for albumin. No adsorption of cytokines was observed. We conclude that cytokine dialysis is achievable through a membrane with a high cut-off point with negligible albumin loss. These findings support the technical feasibility of this new approach to blood purification in sepsis.

Blood Flow Velocity↗
PubMedDate not supplied

Successful pregnancies in dialysis patients including those suffering from cystinosis and familial Mediterranean fever.

For women on maintenance dialysis, pregnancy is still uncommon. The outcome of such pregnancies has improved in recent case series. Here, we report in detail the treatment of five successful pregnancies in dialysis patients from our centre. The present case series also includes the first successful pregnancy of a dialysis patient with underlying familial Mediterranean fever, and of a dialysis patient with cystinosis. We treated all patients with an intensified hemodiafiltration protocol, increased erythropoietin dosages, a generous application of water-soluble vitamins and trace elements in addition to a multidisciplinary clinical management approach with a very low threshold for hospital admission. Specifically, we report treatment of arterial hypertension with respect to changes in dry weight and pharmacological therapy. Mean gestational age at delivery was 32.8+/-3.3 weeks and mean birth weight was 1,765+/-554 g. All mothers and newborns were discharged healthy and in good condition. These modified management guidelines have led to a favourable outcome in all our patients including two patients with familial Mediterranean fever and with cystinosis, and may help to guide therapy in other pregnant dialysis patients.

Adult↗