Use of Therapeutic Apheresis methods in ICU.

Apheresis is a modern medical approach in which plasma or cellular components are separated from the whole blood. Apheresis can be either diagnostic or therapeutic. Diagnostic apheresis is typically applied in hematology and cancer research. Therapeutic Apheresis (TA) includes a broad spectrum of extracorporeal treatments applied in various medical specialties, including Intensive Care Unit (ICU). Considering the complexity of the pathophysiologic characteristics of various clinical entities and in particular sepsis, apheresis methods are becoming increasingly applicable. Therapeutic Plasma Exchange (TPE) is the most common used method in ICU. It is considered as first line therapy for Thrombotic Thrombocytopenic Purpura (TTP) and Guillain Barre Syndrome, while the current data for sepsis are scarce. Over the last decades, technologic evolution has led to increasing application of new and more selective methods based on adsorptive techniques. In this review we will describe the current data of characteristics of different techniques, safety and clinical impact of apheresis methods used in ICUs.

Metabolic acidosis during parenteral nutrition: Pathophysiological mechanisms.

Total parenteral nutrition (TPN) is associated with metabolic complications including metabolic acidosis (MA), one of the main disorders of acid-base balance. The main causes involved in the appearance of MA during TPN administration are the metabolism of cationic amino acids and amino acids containing sulfuric acid (exogenous addition), the titratable acidity of the infused parenteral solution, the addition of acidificant agents (hydrochloric acid, acetic acid), thiamine deficiency, disruption of carbohydrate and lipid metabolic pathways and D-fructose administration. Moreover, hypophosphatemia that appears during TPN therapy contributes significantly to the maintenance of MA. This review describes in a comprehensive way the pathophysiological mechanisms involved in the appearance of MA induced by intravenous administration of TPN products most commonly used in critically ill-patients.

Aliskiren in an alternate-day administration schedule in hypertensive albuminuric patients.

OBJECTIVE: It has been suggested that aliskiren has a long half-life and maintains a blood pressure (BP)-lowering effect following a missed dose. We tested the hypothesis that every other day (eod) administration of aliskiren has the same effects as the once daily (od) dosing in albuminuric hypertensive patients. METHODS: Fifteen hypertensive patients, after a 4-week wash-out period on clonidine, received 300 mg aliskiren od as the sole treatment. In patients who remained out of target, other nonrenin-angiotensin system blockers were added. Patients who completed a 24-week (w24) treatment period were switched to eod administration of aliskiren for an additional period of 24 weeks (w48). RESULTS: Thirteen patients completed the full study protocol. The mean office BP was reduced at the end of w24 (-9/3 mmHg), a reduction that continued to be observed at w48 (-11/1 mmHg). At the end of the study, the 48 h ambulatory BP monitoring was divided into two 24 h periods. The mean 24 h systolic BP, and the mean daytime systolic and diastolic BP were significantly lower (P<0.05) in the first 24 h (when aliskiren was taken) compared with the second period. Central hemodynamics showed no significant differences at any time during monitoring. Administration of aliskiren resulted in a median reduction of urine albumin/creatinine ratio of 103 mg/g (od) and 102 mg/g (eod). Differences in plasma renin activity, plasma renin concentration, and aldosterone-level measurements were not significant. CONCLUSION: The BP-lowering effect of eod aliskiren administration, although adequate, is less efficient compared with od administration, despite the fact that in terms of reducing albuminuria, it appears to be effective.

Differential membrane expression of Toll-like receptors and intracellular cytokine induction in peripheral blood monocytes of patients with chronic kidney disease and diabetic nephropathy.

BACKGROUND: Toll-like receptors (TLRs) are key players in the innate immune system whose activation leads to an inflammatory response. Inflammation plays an important role in the pathogenesis of chronic kidney disease (CKD) and diabetes mellitus. The aim of our study was to assess the proinflammatory state of nondialysis CKD patients by evaluating the membrane expression of TLR2 and TLR4 and the intracellular IL-1ß and IL-6 production in response to the ligand Pam3Cys-Ser-(Lys)4 (Pam3CSK4). METHODS: 85 nondialysis CKD patients [mean estimated glomerular filtration rate: 34 (17-90) ml/min/1.73 m(2)] were divided in 2 groups: 55 nondiabetic CKD patients (CKD group) and 30 patients with diabetic nephropathy (DN group). The two groups were compared with 36 healthy subjects (control group). TLR2 and TLR4 membrane expression in monocytes and Pam3CSK4-induced intracellular production of IL-1ß and IL-6 were assessed by flow cytometry. RESULTS: Both patient groups showed increased TLR2 membrane expression compared with the control group, both at baseline (p < 0.05 for both) and after Pam3CSK4 stimulation (p < 0.05 for both). The DN group exhibited significantly higher TLR4 expression at baseline compared to the CKD and control groups (p < 0.04 and p < 0.02, respectively). Intracellular IL-1ß and IL-6 levels at baseline were significantly lower in CKD patients compared to the DN and control groups. After Pam3CSK4 stimulation, intracellular IL-1ß and IL-6 increased in all groups, but were lower in the CKD group versus the control group or DN group, which exhibited higher levels than the controls. CONCLUSIONS: Nondialysis CKD patients showed significant alterations in TLR2 and TLR4 membrane expression, and impaired Pam3CSK4-induced cytokine production in monocytes, a phenomenon that is markedly influenced by the presence of diabetes.

Mononuclear leukocyte apoptosis and inflammatory markers in patients with chronic kidney disease.

BACKGROUND/AIM: Increased apoptosis along with enhanced inflammation has been reported in hemodialysis and pre-dialysis patients. However, there is limited information at which stage during the progression of chronic kidney disease (CKD) the balance between pro- and anti-apoptotic mechanisms is disturbed and inflammatory response is activated. The aim of this study was to investigate possible alterations in apoptotic and inflammatory markers during CKD (stages 1-4) progression and the probable interactions between them. METHODS: In a cross-sectional study, 152 steady-state CKD outpatients (83 males, 55%) with mean estimated glomerular filtration rate 46 (29-76) ml/min/1.73 m(2) were studied. Apoptosis was assessed in peripheral blood mononuclear cells by estimating Bcl-2 expression, annexin V-propidium iodine staining and serum soluble Fas (sFas) and Fas-ligand. Serum levels of C-reactive protein, tumor necrosis factor-α (TNF-α), interleukin-6 and plasma levels of fibrinogen were measured as markers of inflammation. RESULTS: Bcl-2 expression was found to decrease significantly in both lymphocytes and monocytes from CKD stage 1 to 4. In contrast, the activity of sFas increased significantly and so did the levels of TNF-α and fibrinogen. The majority of these alterations occurred as soon as patients entered stage 3 of CKD. A multivariate regression analysis demonstrated that CKD remained a significant predictor of the aggregate of the assessed markers. CONCLUSIONS: Apoptosis appeared to increase across CKD stages 1-4, and this was associated with increased proinflammatory activity.