Extracorporeal hemoadsorption therapy as a potential therapeutic option for rapid removal of Apixaban in high risk-surgical patients: a case report.

BACKGROUND: Apixaban is a non-vitamin K antagonist oral anticoagulant (NOACs) recently emerged as an effective alternative to conventional vitamin K antagonists (VKAs) in the treatment of several thromboembolic disorders. However, in case of overdose or in patients requiring emergency surgery there is a high bleeding rate and severe adverse side effects due to the absence of an antidote. There is promising data from in vitro and clinical studies, that certain antithrombotic agents (that is Rivaroxaban and Ticagrelor) have been successfully removed by the extracorporeal hemoadsorption therapy CytoSorb. Here, we present the case of a patient successfully treated with CytoSorb as a kind of antidote to enable emergency surgery for bilateral nephrostomy. CASE PRESENTATION: A 82-year-old Caucasian man was admitted to the Emergency Room with acute kidney injury (AKI) in the context of severe bilateral hydroureteronephrosis. The patient's medical history included chronic obstructive pulmonary disease, arterial hypertension, atrial fibrillation (anticoagulated with Apixaban) and a locally advanced prostate adenocarcinoma treated with trans-ureteral resection of the bladder and radiotherapy in the previous months. The indication for a bilateral nephrostomy could not be considered immediately given the major bleeding risk due to Apixaban, which was discontinued and replaced with calciparin. After 36 hours of continuous renal replacement therapy (CRRT), the Apixaban blood level was still elevated and it was decided to install CytoSorb into the running CRRT to accelerate the drug clearance. After 2 hours 30 minutes, there was good reduction of Apixaban from 139 to 72 ng/ml (reduction rate of 48.2%) registered, and this allowed for an easy placement of bilateral nephrostomies without complications. Four days after surgery renal function parameters further normalized, the patient did not require additional dialysis treatments and Apixaban therapy was prescribed again once the patient returned home. CONCLUSIONS: In this case we report the findings of a patient with post-renal AKI requiring emergency nephrostomy placement while on chronic anticoagulation with Apixaban therapy. Combined treatment with CRRT and CytoSorb was associated with the rapid and effective removal of Apixaban allowing for prompt and urgent surgery while simultaneously ensuring the low risk of bleeding as well as an uneventful post-operative course.

Intravenous Iron Replacement Therapy Improves Cardiovascular Outcomes in Hemodialysis Patients.

BACKGROUND/AIM: More than half of deaths among hemodialysis patients are due to cardiovascular disease. This study examined whether intravenous administration of ferric carboxymaltose (FCM) has an impact on cardiovascular events in iron-deficient hemodialysis patients. PATIENTS AND METHODS: We performed a retrospective study concerning patients undergoing hemodialysis in our center from September 2016 to December 2019. We identified those who began FCM therapy (FCM group) during this period and those who did not (control group). We analyzed clinical, echocardiographic and laboratory parameters at the beginning (t0) and after one year (t1), to detect differences between the two groups. RESULTS: We identified 53 patients for the FCM group and 19 for the control group. Median follow-up was 1 year±3 months for both groups. In the FCM group, we observed a reduction in the doses of erythropoiesis-stimulating agents (ESA) (p<0.001) and a significative difference in cardiovascular events (p<0.01), but no differences in echocardiographic parameters. CONCLUSION: Patients who received FCM reached satisfactory values of transferrin saturation and ferritin, presented fewer coronary artery events and cardiovascular events, and could reduce doses of ESA.

Severe quetiapine voluntary overdose successfully treated with a new hemoperfusion sorbent.

Quetiapine overdose, although rare, is mainly linked with tachycardia, QTc-interval prolongation, somnolence, coma, hyperglycemia, and eventually hepatotoxicity and myocarditis. Extracorporeal techniques for quetiapine removal might be helpful, but only a few cases are reported in the literature. We here describe the case of a 27-year-old healthy woman, admitted to our Intensive Care Unit after voluntary quetiapine intake and successfully treated with CytoSorb hemoperfusion in combination with continuous renal replacement therapy (CRRT), in order to accelerate quetiapine elimination. This is the first published experience about the potential application of hemoadsorption therapies, as CytoSorb sorbent, in large overdoses of quetiapine and this approach might be feasible to rapidly remove the substance from blood, stabilizing the patient condition.

Effect of Hemoadsorption for Cytokine Removal in Pneumococcal and Meningococcal Sepsis.

Bacterial meningitis and septicemia are invasive bacterial diseases, representing a significant cause of morbidity and mortality worldwide. Both conditions are characterized by an impressive inflammatory response, resulting rapidly in cerebral edema, infarction, hydrocephalus, and septic shock with multiple organ failure. Despite advances in critical care, outcome and prognosis remain critical. Available adjunctive treatments to control the inflammatory response have shown encouraging results in the evolution of patients with sepsis and systemic inflammation, but meningococcal or pneumococcal infection has not been investigated. We herein report five patients with similar critical pathological conditions, characterized by pneumococcal or meningococcal sepsis and treated with hemoadsorption for cytokine removal. All patients showed a progressive stabilization in hemodynamics along with a rapid and marked reduction of catecholamine dosages, a stabilization in metabolic disorders, and less-than-expected loss of extremities. Therapy proved to be safe and well tolerated. From this first experience, extracorporeal cytokine removal seems to be a valid and safe therapy in the management of meningococcal and pneumococcal diseases and may contribute to the patient stabilization and prevention of severe sequelae. Further studies are required to confirm efficacy in a larger context.

Relationship between coronary artery disease and C-reactive protein levels in NSTEMI patients with renal dysfunction: a retrospective study.

BACKGROUND: While chronic renal damage is a condition with low-grade inflammation, the potential role of inflammation in kidney disease as a marker of cardiovascular damage is of current interest. This study analyzed the relationship between renal dysfunction, chronic inflammation, and extension of coronary atherosclerosis in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS: This retrospective study was carried out on consecutive patients presenting with NSTEMI to Maggiore Hospital's emergency department between January 1, 2010 and December 31, 2011. Patients' electronic charts were reviewed to gather information on patients' history, clinical and biochemical variables, with a special focus on inflammatory markers, coronary vessel damage, and drug treatments. RESULTS: Of the 320 individuals in the study population, 138 (43.1%) had an admission GFR <60 mL/min/1.73 m2. Kidney dysfunction was significantly associated with age (OR = 1.09, 95% CI 1.06 to 1.12), history of heart failure (OR = 2.13, 95% CI 1.08 to 4.17), and hypertension (OR = 2.31, 95% 1.12 to 4.74). C-reactive protein (CRP) and uric acid levels were significantly increased in patients with severe renal dysfunction (SRD) by bivariate and multivariate analyses, adjusted for gender, age and comorbidities at admission. The extent of coronary artery disease (CAD) was significantly higher in the SRD group (p < 0.001). Individuals with SRD were less likely to receive immediate evidence-based therapies (62.9% vs. 76.7% and 82.0% in those with intermediate and no/mild renal dysfunction, p < 0.001). Hospital stay was significantly longer in individuals with a greater extent of CAD, diabetes, and a history of heart failure, and was borderline significantly associated with renal dysfunction (p = 0.08). Older age, CAD severity, and renal function were associated with worsening GFR during hospitalization, whereas immediate evidence-based treatment was unrelated to a GFR change. CONCLUSIONS: Among individuals hospitalized for NSTEMI, those with SRD had a more extensive CAD and a higher prevalence of pre-existing cardiovascular disease. CRP was positively correlated with renal dysfunction and the number of involved coronary vessels, confirming its potential as a biomarker. Uric acid was associated with renal dysfunction but not with the number of diseased coronary vessels.

Incidence and predictors of postoperative atrial fibrillation in kidney transplant recipients.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a complication of cardiothoracic and noncardiothoracic surgery. Kidney transplant recipients bear several known risk factors and may have a higher incidence of POAF. We retrospectively studied kidney and kidney/liver transplant recipients to estimate their POAF incidence and identify relevant risk factors. We also adapted a clinical score originally designed to predict thromboembolic risk in atrial fibrillation (AF; CHA2DS2-VASc) for assessing transplant patients. METHODS: We reviewed the clinical charts of kidney or kidney/liver transplant recipients from January 2005 to December 2008 at St. Orsola University Hospital Kidney Transplant Centre. Patients with and without POAF were compared on a number of clinical, laboratory, and instrumental data. RESULTS: The POAF incidence in kidney transplant recipients was 8.2%. Risk factors for POAF identified in univariate analyses included older recipient age, history of myocardial infarction, history of AF, liver/kidney transplantation, arterial stiffness, atherosclerotic plaques in the aorta or lower limbs, and diabetes mellitus. In a multivariate analysis, age, myocardial infarction history and combined liver/kidney transplantation were significant independent predictors of POAF. The modified CHA2DS2-VASc score proved to have a better predictive validity that the original CHA2DS2-VASc (area under the curve=0.71, 95% confidence interval=0.63-0.79 vs. area under the curve=0.62, 95% confidence interval=0.52-0.73, respectively). CONCLUSION: AF is a notable complication of kidney, and particularly simultaneous liver/kidney, transplant surgery. Age, previous myocardial infarction, and simultaneous liver/kidney transplant independently predicted POAF. The modified CHA2DS2-VASc score could be useful to predict POAF risk in kidney transplant candidates.

Post-coronarography application of continuous veno-venous hemofiltration in the prevention of contrast nephropathy in patients with complex multisystem deficiency.

BACKGROUND: An increased admission of high-risk patients to diagnostic and interventional radiological procedures with contrast medium has resulted in an increase of contrast-induced nephropathy, which now represents the third main cause of hospital-acquired acute renal failure. The pathogenic mechanism of contrast-induced nephropathy (CN) is unclear, but there is much evidence which indicated an interaction between direct tubular cytotoxicity and osmotic/hemodynamic effects. Continuous veno-venous hemofiltration (CVVH) has shown possible benefits in preventing CN. It is not understood when and how prophylactic strategies should be used either in pharmacological therapies or in continous renal replacement therapy (CRRT) approaches. The aim of this study was to evaluate the efficiency of the CVVH technique in preventing CN secondary to emergency radiological procedures in very high-risk patients. PATIENTS AND METHODS: Twelve patients with severe chronic renal impairment (serum creatinine concentration >2 mg/dl with an estimated glomerular filtration rate (eGFR) <40 ml/min) in association with at least two severe comorbidities (such as previous acute myocardial infarction in hypertensive or diabetic patients obesity, cardiac failure with ejection fraction <40%, severe hypotension) were treated with CVVH after coronarography using an iso-osmolar contrast medium (Visipaque, Iodixanol), with or without percutaneous transluminal coronary angioplasty. Adverse events and their association with the interventional radiological procedure were investigated after hemofiltration. RESULTS: Statistically significant differences were observed for both eGFR and serum creatinine at different time points (pre-, post- and 7 days after the procedure) at p<0.05. Statistical analysis of all the variables related to the radiological procedure and the hemofiltration technique did not cause any modification of renal function between the pre- and post-procedure values. No patient showed signs of cardiovascular instability, nor were any episodes of marked hypotension reported during the dialysis session. No patient showed any adverse effects related to the interventional radiological procedure or to the CVVH technique. Renal function, according to serum creatinine concentration and the e-GFR calculation (Cockcroft), did not worsen but had improved when the patients left hospital, with function rates statistically significantly better compared to that on hospital admission, even 7 days after the radiological procedure. CONCLUSION: The present study suggests the efficiency of the CVVH technique in preventing CN in high-risk patients who need to undergo interventional radiological cardiovascular procedures involving the administration of an iodine-based contrast medium.

Tubular dysfunction after peritonectomy and chemohyperthermic treatment with cisplatin.

Peritoneal carcinomatosis has always been regarded as a contraindication in traditional cancer surgery treatment; however, good results have been reported by using new combined medical-surgical loco-regional techniques. Peritonectomy and chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role in obtaining a better survival rate than with the traditional procedures, even though there is a cisplatinum nephrotoxic effect. The aim of this study was to investigate entity and type of renal injury after CIIP. Forty-two patients (12 males and 30 females) with recurrent or primary peritoneal carcinomatosis who underwent peritonectomy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with cisplatin were enrolled. A significant worsening in renal function was observed on the third post-operative day and this condition then persisted for three months. A reduction in estimated-Glomerular Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved tubular injury. On the third post-operative day after cisplatinum administration, a high toxicity peak was found following platinum free fraction excretion. Proximal tubular injury was confirmed even at the three month analysis. A significant correlation between the total protein reduction rate and the decrease in renal function was established. In relation to that, the platinum free fraction could increase because of a binding protein shortage and the nephrotoxic effect could be enhanced due to platinum accumulation within the post-operative period. This finding suggests that the higher the protein reduction is, the lower the e-GFR determination is at three months.

Standard heparin versus low-molecular-weight heparin. A medium-term comparison in hemodialysis.

BACKGROUND: To compare standard heparin (SH) and low molecular weight heparin (LMWH) in terms of anticoagulation, platelet activation and lipid metabolism, we selected 54 patients who had been on 4-hour hemodialysis three times weekly for at least 12 months, without bleeding disorders or dyslipidemic diseases. 28 were on hemodialysis with Polysulfone low-flux, 26 were on hemodiafiltration with Polysulfone high-flux. All patients underwent EPO. METHODS: During the first 18 months, we administered SH 1,500 IU on starting dialysis and 1,500 +/- 500 IU in continuous intradialytic infusion per session. In the following 18 months, we administered LMWH 64.6 IU/kg on starting dialysis in a single arterious bolus. We assessed aPTT, anti-factor Xa activity, TAT and FPA, beta-TG and PF4. Blood samples were taken monthly at times 0, 30, 60, 180 and 240 min, as well as 1, 4 and 20 h after dialysis end. Predialysis cholesterol, HDL, LDL, triglycerides and lipoprotein(a) were checked monthly. RESULTS: During both LMWH and SH sessions no clotting or major bleeding complications were observed. APTT with LMWH was lower than that found with SH (p < 0.001); aFXa using LMWH was higher than when using SH (p < 0.001); TAT and FPA were lower in LMWH sessions (p < 0.01) than in SH sessions. We also detected lower beta-TG (p < 0.05) and PF4 levels (p < 0.05) using LMWH than using SH. As regards lipids, we only observed a significant decrease in triglycerides after 18 months of LMWH treatment. CONCLUSIONS: Routine use of LMWH during hemodialysis affords a safe and effective alternative to SH, and causes reduced platelet activation.