Introduction: Although chronic kidney disease (CKD) is associated with increased risk for coronary artery disease (CAD), the underlying mechanisms are not completely defined. In the present study, we tested the hypothesis that flux of cholesterol from macrophage foam cells to liver is impaired in subjects with CKD. Methods: Consecutive healthy patients, patients with at least 1 CAD risk factor, patients with established CAD, and patients with CKD stages G3 to G5 (n >= 15/group) were recruited prospectively. The ability of total patient serum without any modifications to (i) facilitate efflux of cholesterol from human THP1-macrophage foam cells under physiological conditions (cholesterol efflux capacity [CEC]) and (ii) to deliver this effluxed cholesterol to primary hepatocytes with physiological expression of high-density lipoprotein (HDL) receptor SR-BI (capacity to deliver cholesterol to hepatocytes [CDCH]) was evaluated. Results: Although healthy patients, patients with at least 1 CAD risk factor, and patients with established CAD all showed similar CEC, patients with CKD showed significantly higher CEC. CDCH was significantly lower in all groups compared with the healthy patients; however, when corrected for higher CEC, CDCH in patients with CKD was significantly lower than in patients with CAD. CDCH correlated with age, body mass index, metabolic parameters, inflammatory markers, and kidney function markers (estimated glomerular filtration rate [eGFR], serum creatinine, and serum cystatin C). Conclusions: These results suggest that aberrations in delivery of cholesterol effluxed from macrophage foam cells to liver for final elimination or the last step of reverse cholesterol transport, may underlie the increased risk of CAD in patients with CKD.

Background. The associated increase in the lipopolysaccharide (LPS) levels and uremic toxins in chronic kidney disease (CKD) has shifted the way we focus on intestinal microbiota. This study shows that a disruption of the intestinal barrier in CKD promotes leakage of LPS from the gut, subsequently decreasing insulin sensitivity. Butyrate treatment improved the intestinal barrier function by increasing colonicmucin and tight junction (TJ) proteins. This modulation further ameliorated metabolic functions such as insulin intolerance and improved renal function. Methods. Renal failure was induced by 5/6th nephrectomy (Nx) in rats. A group of Nx and control rats received sodium butyrate in drinking water. The Nx groups were compared with sham-operated controls. Results. The Nx rats had significant increases in serum creatinine, urea and proteinuria. These animals had impaired glucose and insulin tolerance and increased gluconeogenesis, which corresponded with decreased glucagon-like peptide-1 (GLP-1) secretion. The Nx animals suffered significant loss of intestinal TJ proteins, colonic mucin and mucin 2 protein. This was associated with a significant increase in circulating LPS, suggesting a leaky gut phenomenon. 5'adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, known to modulate epithelial TJs and glucose metabolism, was significantly reduced in the intestine of the Nx group. Anti-inflammatory cytokine, interleukin 10, anti-bacterial peptide and cathelicidin-related antimicrobial peptide were also lowered in the Nx cohort. Butyrate treatment increased AMPK phosphorylation, improved renal function and controlled hyperglycemia. Conclusions. Butyrate improves AMPK phosphorylation, increases GLP-1 secretion and promotes colonic mucin and TJ proteins, which strengthen the gut wall. This decreases LPS leakage and inflammation. Taken together, butyrate improves metabolic parameters such as insulin resistance and markers of renal failure in CKD animals.

Current approaches to determine the cause of acute kidney injury (AKI) in patients with cirrhosis are suboptimal. The aim of this study was to determine the utility of fractional excretion of urea (FEUrea) for the differential diagnosis of AKI in patients with cirrhosis. A retrospective analysis was performed in patients (n = 50) with cirrhosis and ascites admitted with AKI. Using adjudicated etiology assessment as the reference standard, receiver operating curves and optimal cutoff, sensitivity (Sn), and specificity (Sp) for the diagnosis of prerenal azotemia (PRA), type 1 hepatorenal syndrome (HRS), and acute tubular necrosis (ATN) were derived. Validation was performed in an independent cohort (n = 50) and by bootstrap analysis. The causes of AKI (derivation:validation cohorts) were: PRA 21:21, HRS 18:15, and ATN 11:14. Median FEUrea was statistically different across all etiologies of AKI in the derivation cohort (PRA 30.1 vs. HRS 20.2 vs. ATN 43.6; P < 0.001) and validation cohort (PRA 23.1 vs. HRS 13.3 vs. ATN 44.7; P < 0.001). The area underneath the curve (cutoff, Sn/Sp) for FEUrea was 0.96 (33.4, 85/100) for ATN versus non‐ATN, 0.87 (28.7, 75/83) for HRS versus non‐HRS, and 0.81 (21.6, 90/61) for PRA versus HRS. When applied to the validation cohort, Sn/Sp were maintained for ATN versus non‐ATN (93/97), HRS versus non‐HRS (100/63), and for PRA versus HRS (67/80). After bootstrapping, Sn/Sp for FEUrea in the ATN versus non‐ATN, HRS versus non‐HRS, and PRA versus HRS was 88/96, 63/97, and 55/87, respectively. Conclusion : FEUrea is a promising tool for the differential diagnosis of AKI in patients with cirrhosis. (H epatology 2018;68:224‐233)

Background: Delayed intensification of blood pressure (BP) management is associated with an increased risk of cardiovascular disease. Pharmacist-physician collaborative care models (PPCMs) improve BP control rates and reduce mean BP, but it is unknown if PPCMs affect time to BP goal when compared to

Hemodialysis (HD) and peritoneal dialysis (PD) are the primary means of managing end stage renal disease (ESRD). However, these treatment modalities are associated with the onset of coagulation abnormalities. Effective management of coagulation risk among these patients requires the identification of surrogate markers that provide an early indication of the coagulation abnormalities. The role of sphingolipids in the manifestation and prediction of coagulation abnormalities among dialysis patients have never been investigated. Herein, we report the first instance of an in depth investigation into the sphingolipid changes among ESRD patients undergoing HD and PD. The results reveal distinct differences in terms of perturbations to specific sphingolipid biosynthetic pathways that are highly dependent on the treatment modality. Our studies also demonstrated strong correlation between specific sphingolipids and coagulation parameters, such as HexCer(d18:1/26:0) and maximal amplitude (MA), SM(d18:1/24:1) and tissue factor pathway inhibitor, and sphingosine 1-phosphate d18:1 and FX (Spearman ρ of 0.93, 0.89, and −0.89, respectively). Furthermore, our study revealed the potential for using HexCer(d18:1/22:0), HexCer(d18:1/24:0), and HexCer(d18:1/26:0) (r2 = 0.71, 0.82, and 0.63, respectively) and coagulation parameter MA (r2 = 0.7) for successful diagnosis of differential coagulopathies among ESRD patients undergoing HD, providing an opportunity toward personalized disease management.

The mechanisms behind the development of hepatic encephalopathy (HE) are unclear, although hyperammonemia and systemic inflammation through gut dysbiosis have been proposed. The aim of this work was to define the individual contribution of hyperammonemia and systemic inflammation on neuroinflammation in cirrhosis using germ‐free (GF) and conventional mice. GF and conventional C57BL/6 mice were made cirrhotic using CCl4 gavage. These were compared to their noncirrhotic counterparts. Intestinal microbiota, systemic and neuroinflammation (including microglial and glial activation), serum ammonia, intestinal glutaminase activity, and cecal glutamine content were compared between groups. GF cirrhotic mice developed similar cirrhotic changes to conventional mice after 4 extra weeks (16 vs. 12 weeks) of CCl4 gavage. GF cirrhotic mice exhibited higher ammonia, compared to GF controls, but this was not associated with systemic or neuroinflammation. Ammonia was generated through increased small intestinal glutaminase activity with concomitantly reduced intestinal glutamine levels. However, conventional cirrhotic mice had intestinal dysbiosis as well as systemic inflammation, associated with increased serum ammonia, compared to conventional controls. This was associated with neuroinflammation and glial/microglial activation. Correlation network analysis in conventional mice showed significant linkages between systemic/neuroinflammation, intestinal microbiota, and ammonia. Specifically beneficial, autochthonous taxa were negatively linked with brain and systemic inflammation, ammonia, and with Staphylococcaceae, Lactobacillaceae, and Streptococcaceae. Enterobacteriaceae were positively linked with serum inflammatory cytokines. Conclusion: Gut microbiota changes drive development of neuroinflammatory and systemic inflammatory responses in cirrhotic animals. (Hepatology 2016;64:1232‐1248)

PURPOSE:To evaluate the effectiveness of a pharmacist-physician collaborative practice model (PPCPM) to improve long-term blood pressure (BP) control rates in a primarily African-American underserved urban population. PRACTICE INNOVATION:Volunteer physicians established initial diagnoses, whereas pharmacists provided most (more than 70%) of the medication management. During each scheduled visit, the pharmacist reconciled the medication list, completed a clinical interview, conducted a focused physical examination, developed and implemented a treatment plan, and provided documentation in a shared medical record. EVALUATION:A retrospective chart review was performed to collect data for a longitudinal cohort of patients managed by the PPCPM from 2010-2013. RESULTS:Of 385 patients with at least two pharmacist visits during 2009, 172 patients received continuous care over the study period. At baseline, the mean age of the cohort was 51.3 years, 62% were female, and 76% were African-American. Approximately 65% were obese (body mass index 30 kg/m(2) or higher), and 39% were cigarette smokers. Mean baseline BP was 156/98 mm Hg, with only 17% of the cohort at their BP goal of lower than 140/90 mm Hg. The BP control rate improved to 66% during the first year and persisted throughout the study period, with 68% of patients at goal in 2013 (p<0.05 compared with baseline). CONCLUSION:The PPCPM BP control rate ranks in the 90th percentile of National Committee for Quality Assurance benchmarks and was superior even to the 2013 reported mean for commercial insurers. The PPCPM effectively improved hypertension control in an uninsured, primarily African-American, urban population despite significant health barriers. Key elements of this asynchronous care model included access to a common medical record, optimization of distinct interprofessional roles, frequent follow-up with evaluation, and collaborative practice agreement with sufficient scope of practice to implement medication changes at the time of the visit.

The reason that determines the pathological deposition of human apolipoprotein A-I variants inducing organ failure has been under research since the early description of natural mutations in patients. To shed light into the events associated with protein aggregation, we studied the structural perturbations that may occur in the natural variant that shows a substitution of a Leucine by an Arginine in position 60 (L60R). Circular dichroism, intrinsic fluorescence measurements, and proteolysis analysis indicated that L60R was more unstable, more sensitive to cleavage and the N-terminus was more disorganized than the protein with the native sequence (Wt). A higher tendency to aggregate was also detected when L60R was incubated at physiological pH. In addition, the small structural rearrangement observed for the freshly folded variant led to the release of tumor necrosis factor-α and interleukin-1β from a model of macrophages. However, the mutant preserved both its dimeric conformation and its lipid-binding capacity. Our results strongly suggest that the chronic disease may be a consequence of the native conformation loss which elicits the release of protein conformations that could be either cytotoxic or precursors of amyloid conformations.

Background & Aims: Infectious acute kidney injury (AKI) is a life threatening complication of cirrhosis with limited therapeutic options. The aim of this study was to develop a model of infectious AKI in cirrhotic mice. Methods: Cirrhosis was established by intragastric administration of carbon tetrachloride (CCl4). Systemic haemodynamics was assessed invasively while cardiac function was assessed by echocardiography. AKI was induced using varying doses of lipopolysaccharide (LPS) titrated to produce 50% lethality. Renal function was assessed from serum creatinine and urine output (UOP). Renal injury was evaluated by urinalysis (proteinuria and casts) and renal histology. These mice were compared to: (i) normal mice, (ii) normal mice + LPS, and (iii) mice treated with CCl4 alone. Results: Cirrhosis with increased cardiac output, decreased systemic vascular resistance, activation of renin-angiotensin-aldosterone axis developed after 12 weeks of CCl4 administration. LPS injection produced a dose-dependent increase in mortality (33% at 2 mg/kg vs. 80% at 6 mg/kg) without urine (casts or proteinuria) or histological evidence of tubular injury. 2 mg/kg LPS injection produced a rise in creatinine (0.79 +/- 0.27 mg/dl in CCl4+LPS compared to 0.45 +/- 0.14 in CCl4 alone, P < 0.05) and a decrease in UOP (0.86 +/- 0.4 ml/16 h in CCl4 + LPS compared to 1.70 +/- 0.7 ml/16 h in CCl4 mice, P < 0.05). UOP remained low in mice that died while it recovered over 4872 h in those that recovered. Control mice treated with 2 mg/kg LPS did not experience AKI. Conclusions: Cirrhotic CCl4 treated mice develop functional AKI and mimic most of the features of infectious AKI following LPS injection.

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham operated animals on normal diet (control) and WD (WD). To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM), a known LPS antagonist, and curcumin (CU), a compound known to ameliorate chronic kidney disease (CKD), was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively). Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.

Cirrhosis is a major contributor to the burden of disease in society, and much of the morbidity and mortality associated with cirrhosis is due to the complications of portal hypertension. Acute kidney injury (AKI) is a frequent complication in patients with cirrhosis, occurring in up to 20 percent of hospitalized patients (1). Despite the high rate of AKI in this patient population, there is often a delay in early diagnosis of AKI. Furthermore, there are clinical challenges in correctly diagnosing the etiology of AKI, which in turn can alter specific therapy. This article will focus on the current pitfalls in diagnosing AKI in cirrhosis and the use of biomarkers in this population. The etiology of AKI in cirrhosis is often separated by functional and structural forms of injury. Approximately one-third of AKI occurrences in hospitalized patients with cirrhosis is from acute tubular necrosis (ATN), although the less common glomerular injury also needs to be screened. The remaining forms of AKI occur from decreased renal perfusion. The majority of these are volumeresponsive prerenal azotemia (PRA), which accounts for approximately 45 percent of the AKI in the cirrhotic population. However, the other third of patients with AKI from decreased renal perfusion are not volume responsive, and have hepatorenal syndrome (HRS) (1). As treatment is different for each of these three types of AKI, the correct diagnosis is imperative. For example, HRS is treated with the vasoconstrictor agents norepinephrine, terlipressin, or midodrine in addition to albumin rescue (2,3). In addition, early diagnosis and subsequent treatment of HRS portends a better renal prognosis (4). The etiology of AKI can also dictate whether renal replacement is offered; specifically, patients not deemed a liver transplant candidate who are diagnosed with HRS are often not offered therapy. However, the converse is true in patients diagnosed with ATN, and missing the diagnosis of ATN can lead to denial of renal support to a patient. Further muddying the picture, infections are common in cirrhotic patients and can independently lead to all three types of AKI (ATN, PRA, and HRS); AKI in these patients may represent a continuum from functional to structural AKI. When a clinician is investigating the etiology of AKI in cirrhosis, common studies used include: serum creatinine, urinalysis evaluation, urine sodium and fractional excretion of sodium (FENA), and urine microscopy evaluation. A percutaneous kidney biopsy could help in the correct diagnosis; however, it is frequently not performed in this patient population because of bleeding concerns. Wadei et al. (5) performed kidney biopsies in cirrhotic patients undergoing a liver transplant and found 41 percent had ATN despite non-classic urinary findings, which highlights the common yet likely underdiagnosed ATN lesion in cirrhosis. As prompt recognition and diagnosis of HRS is crucial in the management of the disease, it is therefore important to know the limitations of current methods to estimate GFR and indices of evaluating AKI. Traditional methods of estimating GFR may be less reliable in cirrhosis compared to the general population, as both urea and creatinine production can be altered in cirrhosis. In addition, cirrhotic patients may have deceivingly low creatinine values, despite the presence of moderate or severe renal failure. This can occur from decreased muscle mass (6), increased renal tubular secretion of creatinine (7), as well as decreased hepatic creatine synthesis. Accordingly, it is well documented that cirrhotic patients can have a normal serum creatinine despite having a truly depressed GFR (6,8). Indeed, both measured as well as calculated creatinine clearances are falsely elevated in cirrhotic patients, and can overestimate inulin clearances by up to 74 percent (9). Traditionally, clinicians have used urine sodium, osmolality, as well as evaluation of urine sediment to help differentiate HRS from other causes of AKI. However, caution should be exercised with these traditional markers of renal function to evaluate the possibility of HRS. For example, patients with ATN in the setting of cirrhosis can have a low urinary sodium concentration, potentially a result from prolonged renal vasoconstriction (10). Conversely, patients with HRS and hyperbilirubinemia can infrequently have high urine sodium values (11,12). Furthermore, granular casts typically associated with ATN can also occur with persistent hyperbilirubinemia in HRS. As a result of these inconsistencies with urinary markers to differentiate ATN from HRS, the International Ascites Club removed these indices with publication of their revised guidelines in 2007 (13). In summary, it is paramount to both diagnose AKI early as well as differentiate structural from a functional type of AKI. Serum creatinine is subject to many pitfalls in cirrhosis, and is also a late marker of kidney injury. Furthermore, it does not segregate between structural and functional AKI, particularly in cirrhosis. To this end, there has been a growing interest in nephrology to find and validate markers of structural kidney injury, especially those that will precede serum creatinine elevations. Interleukin-18 (IL-18), kidney injury molecule-1 (KIM1), liver-type fatty acid binding protein (L-FABP), and neutrophil gelatinase associated lipocalin (NGAL) appear to have the most promise in defining structural, rather than functional, injury in this patient set. Two studies separately investigated the utility of NGAL in differentiating structural (ATN) from functional (PRA or HRS). In the first, Fagundes et al. (14) studied urinary NGAL levels in 241 patients with cirrhosis, 84 of whom had renal dysfunction. They found uNGAL levels were significantly higher in those with ATN compared to PRA or HRS. uNGAL levels in HRS patients were at a level in between ATN and PRA. Moreover, upon review of the HRS cohort, uNGAL levels were higher in patients with an infectious mediated event compared to those who did not have an infection. Moreover, in this subset, uNGAL levels were close to those with ATN. In a second study, Verna et al. (15) measured uNGAL levels in 118 cirrhotic patients admitted to a single hospital. Similar to the preceding study, they also found uNGAL levels significantly higher in patients with intrinsic AKI compared to HRS or PRA, with uNGAL levels in HRS patients intermediate between the two groups. This difference in uNGAL between HRS and intrinsic AKI was in the absence of any difference in serum creatinine. Collectively, these two studies highlighted the promise uNGAL has in differentiating the different forms of AKI. Finally, Belcher et al. (16) evaluated 76 patients with progressive AKI in a prospective, multicenter, blinder study. They found 53 percent had ATN, with the remainder having PRA (26 percent) or HRS (22 percent). FENA was lowest in the cohort diagnosed with HRS, although not statistically different from PRA or ATN. NGAL, L-FABP, IL-18, and KIM-1 were measured in all patients. The etiology of AKI was determined in a blinded manner, without knowledge of the biomarkers. Those identified with ATN had the highest levels of all four biomarkers, with HRS in the intermediate range similar to the two prior studies. Moreover, Belcher et al. found absolute value cutoffs for all four biomarkers to define those with ATN. The relative risk of ATN increased with the increasing number of positive biomarkers. In those patients with none of the four biomarkers above the cutoff, 17 percent had ATN. This increased to 73 percent if two of the biomarkers were positive and to 100 percent if all four were positive. In conclusion, AKI in the cirrhotic population is a frequently encountered clinical problem, and is associated with a high mortality. Because of limitations in available laboratory tests, the diagnosis of AKI is frequently delayed and the etiology of AKI is incorrect. The introduction of new biomarkers that increase earlier than traditional markers, such as serum creatinine, allows for earlier identification of renal injury. Furthermore, these biomarkers hold promise for delineating structural versus functional AKI.

Background: End-stage renal disease patients have significant cardiovascular morbidity and mortality, but little is known about differences in coagulation profiles between patients on hemodialysis (HD) and on peritoneal dialysis (PD). Given their long-term exposure to glucose-based dialysate, patients on PD can experience metabolic derangements. Theoretically, that exposure should create a more prothrombotic environment than occurs in HD patients. The objective of the present study was to quantify potential differences in baseline coagulation between PD and HD patients..Methods: Our single-center cross-sectional study at a large academic health science center enrolled 50 age-, race-, and sex-matched subjects (10 control subjects, 20 HD patients, and 20 PD patients). Measurements included platelet function, platelet receptor distribution, and coagulation dynamics by thromboelastography and Hemodyne hemostasis assay (Hemodyne, Richmond, VA, USA).Results: Compared with healthy control subjects, patients on both forms of dialysis showed prothrombotic coagulation protein profiles. The tissue-factor pathway was markedly elevated in both groups, but PD was associated with significantly greater concentrations of tissue factor (p = 0.0056) and tissue-factor pathway inhibitor (p = 0.0138). Similarly, compared with patients receiving HD, patients on PD had greater concentrations of fibrinogen (p = 0.0325), which corresponded with platelet hyperfunction as measured by platelet contractile force and clot elastic modulus (p = 0.003 and 0.017 respectively, compared with values in HD patients). Platelet receptor distribution was similar between the groups..Conclusions: Compared with patients on HD, patients on PD appear to have a more prothrombotic profile. The clinical relevance of these findings needs to be studied in a prospective manner.

Arteriovenous graft (AVG) thrombosis is a frequent cause of graft failure. We evaluated coagulation protein concentrations, platelet function, and viscoelasticity factors in 20 hemodialysis (HD) patients with AVGs. The goal was to determine whether significant differences in protein concentrations, platelet function, and viscoelasticity factors exist among dialysis patients requiring frequent AVG declot procedures vs. those who do not. Twenty HD patients were enrolled: 10 frequent clotters (>3 declots in the previous year) and 10 were nonclotters. Patients on antiplatelets or chronic anticoagulation were excluded. Laboratories were drawn pretreatment and heparinase was added to counteract any potential heparin effect. Coagulation protein concentrations including tissue factor (TF), thrombin/antithrombin III complex (TAT), and prothrombin fragment 1+2 (F1+2) were assayed. The time to clot onset was measured by force onset time (FOT). Platelet contractile force (PCF) measured the force produced by platelets during clot retraction, whereas clot rigidity was measured as clot elastic modulus (CEM). FOT, CEM, and PCF were measured by Hemodyne. Both groups had upregulation of the TF pathway, as TF, TAT, and F1+2 levels were similarly increased over baseline levels. Hemodialysis patients with frequent AVG clotting had higher levels of both PCF and CEM compared with nonclotters. Additionally, the frequent clotters had a lower FOT relative to nonclotters, although both were considered in the normal range. Our study suggests that HD patients with recurrent AVG thrombotic events form clots with higher tensile strength compared with HD patients without recurrent graft thrombosis.

BACKGROUND & AIMS:Post-paracentesis circulatory dysfunction is associated with development of hepatorenal syndrome and increased mortality. The impact of large volume paracentesis (LVP) on the 24-h blood pressure (BP) profile is unknown, and the relationship to Na+-retentive and pro-inflammatory cytokines also remains unknown. The aims of this study were to (i) define the effects of LVP with albumin administration on 24-h BP profiles, and (ii) relate changes in BP over time to changes in Na+-retentive hormones, clinical factors and inflammatory cytokines. METHODS:Ten patients undergoing LVP had 24-h ambulatory BP monitoring performed pre- and post-paracentesis. Markers of the innate immune system, bacterial translocation and Na+-retentive hormones were drawn pre- and post-LVP. RESULTS:Mean arterial pressure (MAP) dropped in nine of the 10 patients in the 24 h following a paracentesis compared to 24 h preceding the procedure (mean drop of 5.5 mmHg, P<0.005). A mixed effects model was used to define time-covariate interactions in predicting changes in BP profile. Monocyte chemotactic protein-1 (MCP1) was associated with Δsystolic BP (β=-0.011, P<0.05), Δdiastolic BP (β=-0.012, P<0.05) and ΔMAP (β=-0.012, P<0.05). Plasma renin activity was also significantly associated with Δsystolic BP (β=-0.21, P<0.05). Renal function was also significantly reduced following LVP. CONCLUSIONS:Systolic, diastolic and MAP decreased over 24 h after LVP compared to the 24 h pre-LVP. This drop is related to increases in MCP-1 after LVP. Increased MCP-1, a marker of monocyte activation, was strongly related to changes in BP.