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Papers by Balàzs Szamosfalvi

Research paper thumbnail of System and Method for Delivery of Regional Citrate Anticoagulation to Extracorporeal Blood Circuits

Research paper thumbnail of Treatment of severe metabolic alkalosis with continuous renal replacement therapy: bicarbonate kinetic equations of clinical value

ASAIO journal (American Society for Artificial Internal Organs : 1992), Jan 24, 2015

Concomitant severe metabolic alkalosis, hypernatremia and kidney failure pose a therapeutic chall... more 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 (CRRT) with delivered hourly urea clearance of ~3 L/h (24-hour sustained low efficiency dialysis with regional citrate anticoagulation [SLED-RCA] 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 mE...

Research paper thumbnail of Online Hemoglobin and Oxygen Saturation Sensing during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

ASAIO Journal, 2014

Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in combination with othe... more 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 pre-dialyzer into the extracorporeal circuit of continuous renal replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hour CRRT systems, clotting in the optical blood chamber and the pre-sensor dilution incurred by replacement fluid should be minimized. Sustained low efficiency dialysis (SLED) with regional citrate anticoagulation (RCA) is a therapy which incorporates an OHOS and maintains the overall reliability of hemoglobin 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 pre-sensor dilution incurred by concentrated citrate infusion, would result in a minimal hemoglobin dilution (<0.7 g/dl) while minimizing optical blood chamber clotting during 24-hour SLED.

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

American Journal of Kidney Diseases, 2014

Patients with hypervolemic hyponatremia and kidney failure pose a special therapeutic challenge. ... more 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.

Research paper thumbnail of A New Mesangial Triumvirate: Sulfonylureas, Their Receptors and Endosulfines

Nephron Experimental Nephrology, 2002

Although sulfonylureas have long been therapeutically utilized for their hypoglycemic properties ... more 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.

Research paper thumbnail of Development of an online citrate/Ca2+ sensing system for dialysis

The Analyst, 2011

An online citrate and Ca(2+) sensing system based on sequential injection analysis (SIA) is devel... more An online citrate and Ca(2+) sensing system based on sequential injection analysis (SIA) is developed as a safety module for hemodialysis. Host 1 displays high affinity towards citrate, and was selected for this study owing to its unique structural features. The o-aminomethylphenylboronic moiety can effectively interact with the α-hydroxycarboxylate moiety of citrate and the remaining two guanidiniums may further stabilize the complex via hydrogen bonds. Fura-2 chelates to Ca(2+) with a high selectivity and affinity and was utilized in this study for Ca(2+) measurements. The citrate sensing chemistry via an indicator displacement assay is orthogonal to the Ca(2+) sensing chemistry, and the use of sophisticated chemometrics is not required for data analysis. The citrate and Ca(2+) concentrations in dialysate samples are measured with the developed SIA system. The obtained citrate concentrations were verified via a commercially available enzymatic assay and an NMR method, respectively, while the Ca(2+) concentrations were verified via atomic absorption.

Research paper thumbnail of Putative subunits of the rat mesangial KATP: A type 2B sulfonylurea receptor and an inwardly rectifying K+ channel

Kidney International, 2002

Complementary studies showed abundant gene expression of Putative subunits of the rat mesangial K... more Complementary studies showed abundant gene expression of Putative subunits of the rat mesangial K ATP : A type 2B sulfonyl-Kir6.1, thereby establishing gene expression of both compourea receptor and an inwardly rectifying K ؉ channel.

Research paper thumbnail of Characterization of the rat mesangial cell type 2 sulfonylurea receptor

Kidney International, 1999

pancreatic ␤ cells as insulin secretagogues [3]. However, receptor.

Research paper thumbnail of Rat mesangial alpha-endosulfine

Kidney International, 2004

Background. Sulfonylurea agents exert their physiologic effects via binding to specific sulfonylu... more Background. Sulfonylurea agents exert their physiologic effects via binding to specific sulfonylurea receptors (SUR) in adenosine triphosphate-sensitive potassium (K ATP ) channels. Mesangial cells express K ATP and respond to sulfonylureas by altering glucose metabolism, elevating intracellular calcium and contracting. A putative endogenous sulfonylurea, a-endosulfine, has been demonstrated in diverse tissues and is a member of the cyclic adenosine monophosphate (cAMP)regulated family of phosphoproteins. This study investigates mesangial cell expression of ENSA, the gene encoding aendosulfine, and its regulation by glucose.

Research paper thumbnail of Automated Regional Citrate Anticoagulation: Technological Barriers and Possible Solutions

Blood Purification, 2010

Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the techn... more 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. 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 Q(B) = 200 ml/min for blood; Q(D) = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO(3) = 32 mmol/l; Q(citrate) = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The Q(Ca) was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. 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 (Q(Ca)) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The Q(Ca) 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. Using predictive Q(Ca) 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.

Research paper thumbnail of Considerations in the Critically Ill ESRD Patient

Advances in Chronic Kidney Disease, 2013

ESRD patients are admitted more frequently to intensive care units (ICUs) and have higher mortali... more 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.

Research paper thumbnail of System and Method for Delivery of Regional Citrate Anticoagulation to Extracorporeal Blood Circuits

Research paper thumbnail of Treatment of severe metabolic alkalosis with continuous renal replacement therapy: bicarbonate kinetic equations of clinical value

ASAIO journal (American Society for Artificial Internal Organs : 1992), Jan 24, 2015

Concomitant severe metabolic alkalosis, hypernatremia and kidney failure pose a therapeutic chall... more 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 (CRRT) with delivered hourly urea clearance of ~3 L/h (24-hour sustained low efficiency dialysis with regional citrate anticoagulation [SLED-RCA] 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 mE...

Research paper thumbnail of Online Hemoglobin and Oxygen Saturation Sensing during Continuous Renal Replacement Therapy with Regional Citrate Anticoagulation

ASAIO Journal, 2014

Optical hemoglobin and oxygen saturation sensor (OHOS) monitor when used in combination with othe... more 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 pre-dialyzer into the extracorporeal circuit of continuous renal replacement therapy (CRRT) systems. To maximize the accuracy of the OHOS in 24 hour CRRT systems, clotting in the optical blood chamber and the pre-sensor dilution incurred by replacement fluid should be minimized. Sustained low efficiency dialysis (SLED) with regional citrate anticoagulation (RCA) is a therapy which incorporates an OHOS and maintains the overall reliability of hemoglobin 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 pre-sensor dilution incurred by concentrated citrate infusion, would result in a minimal hemoglobin dilution (<0.7 g/dl) while minimizing optical blood chamber clotting during 24-hour SLED.

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

American Journal of Kidney Diseases, 2014

Patients with hypervolemic hyponatremia and kidney failure pose a special therapeutic challenge. ... more 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.

Research paper thumbnail of A New Mesangial Triumvirate: Sulfonylureas, Their Receptors and Endosulfines

Nephron Experimental Nephrology, 2002

Although sulfonylureas have long been therapeutically utilized for their hypoglycemic properties ... more 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.

Research paper thumbnail of Development of an online citrate/Ca2+ sensing system for dialysis

The Analyst, 2011

An online citrate and Ca(2+) sensing system based on sequential injection analysis (SIA) is devel... more An online citrate and Ca(2+) sensing system based on sequential injection analysis (SIA) is developed as a safety module for hemodialysis. Host 1 displays high affinity towards citrate, and was selected for this study owing to its unique structural features. The o-aminomethylphenylboronic moiety can effectively interact with the α-hydroxycarboxylate moiety of citrate and the remaining two guanidiniums may further stabilize the complex via hydrogen bonds. Fura-2 chelates to Ca(2+) with a high selectivity and affinity and was utilized in this study for Ca(2+) measurements. The citrate sensing chemistry via an indicator displacement assay is orthogonal to the Ca(2+) sensing chemistry, and the use of sophisticated chemometrics is not required for data analysis. The citrate and Ca(2+) concentrations in dialysate samples are measured with the developed SIA system. The obtained citrate concentrations were verified via a commercially available enzymatic assay and an NMR method, respectively, while the Ca(2+) concentrations were verified via atomic absorption.

Research paper thumbnail of Putative subunits of the rat mesangial KATP: A type 2B sulfonylurea receptor and an inwardly rectifying K+ channel

Kidney International, 2002

Complementary studies showed abundant gene expression of Putative subunits of the rat mesangial K... more Complementary studies showed abundant gene expression of Putative subunits of the rat mesangial K ATP : A type 2B sulfonyl-Kir6.1, thereby establishing gene expression of both compourea receptor and an inwardly rectifying K ؉ channel.

Research paper thumbnail of Characterization of the rat mesangial cell type 2 sulfonylurea receptor

Kidney International, 1999

pancreatic ␤ cells as insulin secretagogues [3]. However, receptor.

Research paper thumbnail of Rat mesangial alpha-endosulfine

Kidney International, 2004

Background. Sulfonylurea agents exert their physiologic effects via binding to specific sulfonylu... more Background. Sulfonylurea agents exert their physiologic effects via binding to specific sulfonylurea receptors (SUR) in adenosine triphosphate-sensitive potassium (K ATP ) channels. Mesangial cells express K ATP and respond to sulfonylureas by altering glucose metabolism, elevating intracellular calcium and contracting. A putative endogenous sulfonylurea, a-endosulfine, has been demonstrated in diverse tissues and is a member of the cyclic adenosine monophosphate (cAMP)regulated family of phosphoproteins. This study investigates mesangial cell expression of ENSA, the gene encoding aendosulfine, and its regulation by glucose.

Research paper thumbnail of Automated Regional Citrate Anticoagulation: Technological Barriers and Possible Solutions

Blood Purification, 2010

Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the techn... more 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. 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 Q(B) = 200 ml/min for blood; Q(D) = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO(3) = 32 mmol/l; Q(citrate) = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The Q(Ca) was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. 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 (Q(Ca)) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The Q(Ca) 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. Using predictive Q(Ca) 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.

Research paper thumbnail of Considerations in the Critically Ill ESRD Patient

Advances in Chronic Kidney Disease, 2013

ESRD patients are admitted more frequently to intensive care units (ICUs) and have higher mortali... more 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.