Balazs Szamosfalvi

Automated regional citrate anticoagulation: technological barriers and possible solutions.

Background: Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the technique as practiced traditionally. Safe RCA protocols with automated delivery on customized dialysis systems are needed. Methods: We applied kinetic analysis of solute fluxes during RCA to design a protocol for sustained low-efficiency dialysis (SLED) for critically ill patients. We used a high-flux hemodialyzer, a zero-calcium (Ca) dialysate, a dialysis machine with online clearance and access recirculation monitoring, and a separate optical hematocrit (Hct) sensor. Flow rates were QB = 200 ml/min for blood; QD = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO3 = 32 mmol/l; Qcitrate = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The QCa was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. Results: Using the SLED-RCA protocol in an anhepatic, ex vivo dialysis system, ionized Ca (iCa) was >1 mmol/l in the blood reservoir and <0.3 mmol/l in the blood circuit after citrate but before Ca infusion (QCa) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The QCa prediction algorithm maintained normal systemic iCa (0.95–1.4 mmol/l) in all patients. The high citrate extraction on the dialyzer prevented systemic citrate accumulation even in shock liver patients. Safety analysis shows that building a dialysis system for automated SLED-RCA is feasible. Conclusion: Using predictive QCa dosing and integrating control of the infusion pumps with the dialysis machine, SLED-RCA can be near-automated today to provide a user-friendly and safe system.

Treatment of Severe Hyponatremia in Patients With Kidney Failure: Role of Continuous Venovenous Hemofiltration With Low-Sodium Replacement Fluid

Patients with hypervolemic hyponatremia and kidney failure pose a special therapeutic challenge. Hemodialysis to correct volume overload, azotemia, and abnormal electrolyte levels will result in rapid correction of serum sodium concentration and place the patient at risk for osmotic demyelination syndrome. We present a patient with acute kidney injury and severe hypervolemic hypotonic hyponatremia (serum sodium<100 mEq/L) who was treated successfully with continuous venovenous hemofiltration. This teaching case illustrates the limitations of hemodialysis and demonstrates how to regulate the sodium correction rate by single-pool sodium kinetic modeling during continuous venovenous hemofiltration. Two methods to adjust the replacement fluid to achieve the desired sodium concentration are outlined.

Sensors and hybrid therapies: a new approach with automated citrate anticoagulation.

Background: Hybrid therapies use intermittent hemodialysis (IHD) machines adapted to provide prolonged intermittent or continuous renal replacement therapy in the intensive care unit (ICU). Despite the low cost, hybrid therapy use is limited warranting a novel approach. Methods: The literature was reviewed for limitations of hybrid protocols, use of regional citrate anticoagulation (RCA) on hybrid systems and sensors for IHD and hybrid therapy. The novel hybrid program in the authors’ institution is presented as a plausible future direction for the modality. Results: Hybrid therapies are limited by access flow and clotting alarms. Technology limitations render many IHD sensors inoperable at low dialysate flow. A synergy with RCA allows a novel, safe approach with low blood flows and high dialysate flows with alarm- and clotting-free operation and all commercial IHD sensors functional. Conclusion: The low cost, ease of use, safety and efficacy of hybrid therapy with near-automated RCA may lead to rapid expansion of this form of ICU renal support.

A multi-center, randomized, controlled, pivotal study to assess the safety and efficacy of a selective cytopheretic device in patients with acute kidney injury

Objective Acute kidney injury (AKI) is a highly morbid condition in critically ill patients that is associated with high mortality. Previous clinical studies have demonstrated the safety and efficacy of the Selective Cytopheretic Device (SCD) in the treatment of AKI requiring continuous renal replacement therapy in the intensive care unit (ICU). Design, Setting, Patients A randomized, controlled trial of 134 ICU patients with AKI, 69 received continuous renal replacement therapy (CRRT) alone and 65 received SCD therapy. Results No significant difference in 60-day mortality was observed between the treated (27/69; 39%) and control patients (21/59; 36%, with six patients lost to follow up) in the intention to treat (ITT) analysis. Of the 19 SCD subjects (CRRT+SCD) and 31 control subjects (CRRT alone) who maintained a post-filter ionized calcium (iCa) level in the protocol’s recommended range (≤ 0.4mmol/L) for greater or equal to 90% of the therapy time, 60-day mortality was 16% (3/19) in the SCD group compared to 41% (11/27) in the CRRT alone group (p = 0.11). Dialysis dependency showed a borderline statistically significant difference between the SCD treated versus control CRRT alone patients maintained for ≥ 90% of the treatment in the protocol’s recommended (r) iCa target range of ≤ 0.4 mmol/L with values of, 0% (0/16) and 25% (4/16), respectively (P = 0.10). When the riCa treated and control subgroups were compared for a composite index of 60 day mortality and dialysis dependency, the percentage of SCD treated subjects was 16% versus 58% in the control subjects (p<0.01). The incidence of serious adverse events did not differ between the treated (45/69; 65%) and control groups (40/65; 63%; p = 0·86). Conclusion SCD therapy may improve mortality and reduce dialysis dependency in a tightly controlled regional hypocalcaemic environment in the perfusion circuit. Trial Registration ClinicalTrials.gov NCT01400893 http://clinicaltrials.gov/ct2/show/NCT01400893

Continuous Renal Replacement Therapy for the Management of Acid-Base and Electrolyte Imbalances in Acute Kidney Injury

Continuous renal replacement therapy (CRRT) is used to manage electrolyte and acid-base imbalances in critically ill patients with acute kidney injury. Although a standard solution and prescription is acceptable in most clinical circumstances, specific disorders may require a tailored approach such as adjusting fluid composition, regulating CRRT dose, and using separate intravenous infusions to mitigate and correct these disturbances. Errors in fluid prescription, compounding, or delivery can be rapidly fatal. This article provides an overview of the principles of acid-base and electrolyte management using CRRT.

Considerations in the Critically Ill ESRD Patient

ESRD patients are admitted more frequently to intensive care units (ICUs) and have higher mortality risks than the general population, and the main causes of critical illness among ESRD patients are cardiovascular events, sepsis, and bleeding. Once in the ICU, hemodynamic stabilization and fluid-electrolyte management pose major challenges in oligoanuric patients. Selection of renal replacement therapy (RRT) modality is influenced by the outpatient modality and access, as well as severity of illness, renal provider experience, and ICU logistics. Currently, most patients receive intermittent hemodialysis or continuous RRT with temporary vascular access catheters. Acute peritoneal dialysis (PD) is less frequently utilized, and utility of outpatient PD is reduced after an ICU admission. Thus, preservation of current vascular accesses, while limiting venous system damage for future access creations, is relevant. Also, dosing of small-solute clearance with urea kinetic modeling is difficult and may be supplanted by novel online clearance techniques. Medication dosing, coordinated with delivered RRT, is essential for septic patients treated with antibiotics. A comprehensive, standardized approach by a multidisciplinary team of providers, including critical care specialists, nephrologists, and pharmacists, represents a nexus of care that can reduce readmission rates, morbidity, and mortality of vulnerable ESRD patients.

Immunomodulatory Device Promotes a Shift of Circulating Monocytes to a Less Inflammatory Phenotype in Chronic Hemodialysis Patients

Patients with end-stage renal disease (ESRD) on chronic hemodialysis (HD) suffer accelerated morbidity and mortality rates caused by cardiovascular disease and infections. Chronic inflammation plays a critical role in these poor outcomes. The activated monocyte (MO) has become a prime therapeutic target to modulate this inflammatory process. A selective cytopheretic device (SCD) was evaluated to assess its effects on the circulating MO pool. A pilot trial was undertaken in 15 ESRD patients on HD with C-reactive protein (CRP) levels greater than 5u2009mg/dl. An excellent safety profile was observed with no decline in leukocyte (LE) or platelet counts. The effect of SCD therapy on MO phenotypes in these patients was determined on peripheral blood MO utilizing flow cytometry. SCD therapy promoted a shift in MO phenotype from predominantly CD14hi expressing MO at baseline/pre-SCD therapy to CD14low expressing MO post-SCD therapy. A significant shift in MO population phenotype afforded by a single SCD therapy session was observed (p < 0.013). In a subset of patients (n = 7) presenting with type 2 diabetes mellitus (T2D), this persistent decline in MO CD14 expression was sustained as long as 2 weeks posttherapy. These results demonstrate that the SCD therapy has the potential to modulate the chronic proinflammatory state in ESRD patients.

Online Hemoglobin and Oxygen Saturation Sensing During Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation.

Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in combination with other hemodynamic tools may be useful for continuous hemodynamic monitoring during ultrafiltration. The stand-alone OHOS monitor can easily be deployed predialyzer into the extracorporeal circuit of continuous renal replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hr CRRT systems, clotting in the optical blood chamber and the presensor dilution incurred by replacement fluid should be minimized. Sustained low-efficiency dialysis (SLED) with regional citrate anticoagulation is a therapy that incorporates an OHOS and maintains the overall reliability of hemoglobin (Hb) and saturation sensing. The system operates at a blood flow rate of 60 ml/min and a fixed acid citrate infusion rate of 150 ml/hr. The presensor dilution incurred by concentrated citrate infusion would result in a minimal Hb dilution (<0.7 g/dl) while minimizing optical blood chamber clotting during 24 hr SLED.

Treatment of Severe Metabolic Alkalosis with Continuous Renal Replacement Therapy: Bicarbonate Kinetic Equations of Clinical Value.

Concomitant severe metabolic alkalosis, hypernatremia, and kidney failure pose a therapeutic challenge. Hemodialysis to correct azotemia and abnormal electrolytes results in rapid correction of serum sodium, bicarbonate, and urea but presents a risk for dialysis disequilibrium and brain edema. We describe a patient with Zollinger-Ellison syndrome with persistent encephalopathy, severe metabolic alkalosis (highest bicarbonate 81 mEq/L), hypernatremia (sodium 157 mEq/L), and kidney failure despite 30 hours of intravenous crystalloids and proton pump inhibitor. We used continuous renal replacement therapy (RRT) with delivered hourly urea clearance of ~3 L/hour (24 hour sustained low efficiency dialysis with regional citrate anticoagulation protocol at blood flow rate 60 ml/min and dialysate flow rate 400 ml/min). To mitigate a pronounced decrease in plasma osmolality while removing urea from this hypernatremic patient, dialysate sodium was set to start at 155 mEq/L then at 150 mEq/L after 6 hours. Serum bicarbonate, urea, and sodium were slowly corrected over 26 hours. This case demonstrates how to regulate and predict the systemic bicarbonate level using single pool kinetic modeling during convective or diffusive RRT. Kinetic modeling provides a valuable tool for systemic blood pH control in future combined use of extracorporeal CO2 removal and continuous RRT systems.

A New Mesangial Triumvirate: Sulfonylureas, Their Receptors and Endosulfines

Although sulfonylureas have long been therapeutically utilized for their hypoglycemic properties in type 2 diabetic patients, there is a paucity of clinical or experimental data that suggests that this pharmacotherapeutic class confers a benefit on the course of diabetic renal disease. Because the mesangial compartment is central to the fibrogenic response that evolves during the course of diabetic nephropathy, determining the metabolic influence of sulfonylureas on mesangial cells is important. In this article, the current knowledge regarding the metabolic and functional consequences of a mesangial triumvirate of sulfonylureas, their sulfonylurea receptors and sulfonylurea-like ligands termed endosulfines will be reviewed.