Background The most common configuration for arteriovenous fistula is brachiocephalic which often... more Background The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. Methods Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shea...
Background The most common configuration for arteriovenous fistula is brachiocephalic which often... more Background The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. Methods Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shea...
Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nu... more Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. How these nascent crystals are retained in the nephron to form calculi in certain individuals is not known. Recent studies from this laboratory have demonstrated that COM crystals can bind within seconds to the apical surface of renal epithelial cells, suggesting one mechanism whereby crystals could be retained in the tubule. Adherence of crystals to cells along the nephron may be opposed by specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, and citrate. In culture, adherent crystals are quickly internalized by renal cells, and reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation can ensue. Each of these cellular events appears to be regulated by extracellular factors. Identification of molecules in tubular fluid and on the cell surface that determine whether a crystal-cell interaction results in retention of the crystal or its passage out of the nephron appears critical for understanding the pathogenesis of nephrolithiasis.
Renal cell osteopontin production is stimulated by calcium oxalate monohydrate crystals. Specific... more Renal cell osteopontin production is stimulated by calcium oxalate monohydrate crystals. Specific anions in tubular fluid, including uropontin (UP), the urinary form of human osteopontin (OPN), block adhesion to renal tubular cells of the most common crystal in kidney stones, calcium oxalate monohydrate (COM). In this study, monkey renal epithelial cells (BSC-1 line) in monolayer culture constitutively secreted UP into the culture medium. COM crystals added to the medium avidly bound previously secreted UP, reducing its concentration by 46% one hour later. However, the net UP content of cultures after a 24-hour exposure to COM crystals was increased by 18%. Northern blotting showed that the constitutively expressed gene encoding human OPN was maximally stimulated in BSC-1 cells after exposure to COM crystals for 12 hours. Two other calcium-containing crystals, hydroxyapatite and brushite, did not alter OPN gene expression or protein production. OPN mRNA expression was enhanced in canine renal epithelial cells (MDCK line) after exposure to COM crystals for six hours, whereas the constitutive expression of murine OPN mRNA by 3T3 fibroblasts was unchanged. In vivo this glycoprotein could defend the cell against adhesion of crystals in tubular fluid, and/or promote renal interstitial fibrosis in subjects with heavy ciystalluria. Urine is usually supersaturated with calcium and oxalate ions that nucleate to form calcium oxalate crystals [1]. The fate of newly-formed crystals in the nephron is not clear. Once formed a crystal could either grow large enough to occlude the tubule lumen, aggregate with other crystals to form a mass large enough to do so, or adhere to the tubular epithelium; otherwise it would be swept out of the nephron in the flowing fluid within a few minutes. Although growth, aggregation, and cell adhesion may contribute to crystal retention in the nephron, cell-crystal interactions have not been as extensively studied as the former two processes. Crystals of calcium oxalate monohydrate (COM) that form in tubular fluid can bind to the apical surface of cultured renal epithelial cells and become internalized [2-51, thereby stimulating an array of responses including proliferation [6-9]. Cell-crystal interactions in vivo could lead to crystal retention in the kidney and the development of nephrolithiasis, and/or promote interstitial fibrosis and scarring in subjects with excessive crystalluria as occurs in primary hyperoxaluria [8]. We have employed cultures of renal epithelial cells (BSC-i and MDCK lines) and COM crystals as a model system to study the
Word Count: 319 Corresponding Authors: Mary Hammes, DO Associate Professor of Medicine University... more Word Count: 319 Corresponding Authors: Mary Hammes, DO Associate Professor of Medicine University of Chicago 5841 S Maryland Ave., MC-5100 Chicago, IL 60637 [email protected] Phone: 773-702-9892 Fax: 773-753-8301 Anindita Basu, PhD Assistant Professor of Medicine University of Chicago 5841 South Maryland Ave., N417B Chicago, IL 60637 [email protected] Phone: 7738341512 This publication was made possible by the National Institute of Diabetes and Digestive Diseases (NIDDK) and the National Institutes of Health (NIH) under award number RO1DK090769. The study was approved by the Institutional Review Board from the University of Chicago (Protocol number: 11-0269) on August 10, 2011. No conflicts of interest, financial or otherwise, are declared by the author(s). The authors thank all subjects for participation in the study.
International Journal of Nephrology and Kidney Failure, 2017
Background-Vascular access for hemodialysis is best provided by an arteriovenous fistula (AVF). A... more Background-Vascular access for hemodialysis is best provided by an arteriovenous fistula (AVF). AVF fail primarily because of neointimal hyperplasia. Asymmetric dimethlyarginine (ADMA) is a naturally occurring analogue of L-arginine, which is elevated in renal failure and impairs endothelial cell function. ADMA inhibits nitric oxide synthetase, leading to impaired nitric oxide production and contributing to the development of neointimal hyperplasia. ADMA was measured at the time of AVF placement to evaluate associations with access failure. Methods-ADMA was measured at the time of brachiocephalic access placement. Patients were followed for up to 12 months with end-points of access thrombosis or venous stenosis. Results-Sixty patients with primary brachiocephalic fistulas were included in the study cohort. The median value for ADMA drawn at the time of AVF creation was 3.1 µmol/L. ADMA was not significantly associated with early thrombosis or venous stenosis events (P>0.05). Conclusion-Preoperative ADMA levels, as a surrogate for endothelial cell dysfunction and predictor of adverse access event (thrombosis or stenosis), were not associated with subsequent access events Future studies that identify markers of endothelial cell dysfunction are warranted.
The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vas... more The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vascular access. Although a variety of access options are available, the arteriovenous fistula remains the best vascular access. Unfortunately the success rate of mature fistula use remains poor. The creation of an arteriovenous fistula is followed by altered hemodynamic and biological changes that may result in neointimal hyperplasia and eventual venous stenosis. This review provides an overview of these changes and the needed research to provide a long lasting vascular access and hence improve outcomes for patients with end-stage renal disease.
Background. The authors measured urine and blood stone risk factors in African-American (AA) haem... more Background. The authors measured urine and blood stone risk factors in African-American (AA) haemodialysis (HD) patients with new onset of stones during dialysis. Methods. Patients with nephrolithiasis (NL) newly manifested during dialysis were matched by age, sex and urine output and dialysis duration to AA HD patients without history or symptoms of stones. Two 24 h urine and serum samples were collected and analysed for conventional stone risk factors. Results. Three percent of the patients formed new stones while on HD; none had formed stones prior to end-stage renal disease. Newly onset NL patients had higher urine citrate and lower serum potassium levels than HD patients without stones. Conclusion. Usual stone risk factors did not correlate with new stones during dialysis.
... Alternatively Spliced Human Tissue Factor and Thrombotic Tendencies in Hemodialysis Patients ... more ... Alternatively Spliced Human Tissue Factor and Thrombotic Tendencies in Hemodialysis Patients Susan Zawaski1, Mary Hammes2*, Viji Balasubramanian1 ... Plasma asHTF levels were quantified and then compared to a variety of patient parameters collected for each patient. ...
Vascular access maintenance is crucial to providing adequate hemodialysis (HD) and hence preventi... more Vascular access maintenance is crucial to providing adequate hemodialysis (HD) and hence preventing signs and symptoms of uremia. The best vascular assess is a permanent arteriovenous fistula (AVF) because it has the longest survival with the least number of complications. However, because of problems with AVF maturation, the majority of HD in the United States is provided via an arteriovenous graft (AVG) or tunneled cuffed central venous catheter. The most common access complications include infection and thrombosis. For these reasons, a patient is often referred to interventional radiology for a procedure such as a catheter placement, change, or a thrombectomy with angioplasty and/or stent placement. Commonly, a HD patient will present after missing a dialysis session. This might predispose the patient to further complications. This review is intended to provide insight into some of the common medical problems (infectious, hematologic, and cardiac) facing a HD patient as a consequence of uremia. Increased awareness to these medical issues provides guidance to prevent unnecessary complications in this difficult patient population.
High flow arteriovenous fistulas are a common clinical entity affecting patients with end-stage r... more High flow arteriovenous fistulas are a common clinical entity affecting patients with end-stage renal failure receiving hemodialysis. Given the difficulty in predicting who will develop a high flow arteriovenous fistula the exact prevalence is unclear. We present two cases of patients with high flow arteriovenous fistula that developed clinical cardiac failure at a time point after the fistula was placed with findings of significant cephalic arch stenosis. Both patients required treatment of cephalic arch stenosis with balloon angioplasty with subsequent surgical aneurism resection. Accurate and timely diagnosis of high flow arteriovenous hemodynamics by prospective monitoring of volumetric flow and cardiac function is required to halt this process prior to cardiac compromise.
Accurate intravascular volume assessment is critical in the treatment of patients who receive chr... more Accurate intravascular volume assessment is critical in the treatment of patients who receive chronic hemodialysis (HD) therapy. Clinically assessed dry weight is a poor surrogate of intravascular volume; however, ultrasound assessment of the inferior vena cava (IVC) is an effective ...
Background The most common configuration for arteriovenous fistula is brachiocephalic which often... more Background The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. Methods Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shea...
Background The most common configuration for arteriovenous fistula is brachiocephalic which often... more Background The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. Methods Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shea...
Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nu... more Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. How these nascent crystals are retained in the nephron to form calculi in certain individuals is not known. Recent studies from this laboratory have demonstrated that COM crystals can bind within seconds to the apical surface of renal epithelial cells, suggesting one mechanism whereby crystals could be retained in the tubule. Adherence of crystals to cells along the nephron may be opposed by specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, and citrate. In culture, adherent crystals are quickly internalized by renal cells, and reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation can ensue. Each of these cellular events appears to be regulated by extracellular factors. Identification of molecules in tubular fluid and on the cell surface that determine whether a crystal-cell interaction results in retention of the crystal or its passage out of the nephron appears critical for understanding the pathogenesis of nephrolithiasis.
Renal cell osteopontin production is stimulated by calcium oxalate monohydrate crystals. Specific... more Renal cell osteopontin production is stimulated by calcium oxalate monohydrate crystals. Specific anions in tubular fluid, including uropontin (UP), the urinary form of human osteopontin (OPN), block adhesion to renal tubular cells of the most common crystal in kidney stones, calcium oxalate monohydrate (COM). In this study, monkey renal epithelial cells (BSC-1 line) in monolayer culture constitutively secreted UP into the culture medium. COM crystals added to the medium avidly bound previously secreted UP, reducing its concentration by 46% one hour later. However, the net UP content of cultures after a 24-hour exposure to COM crystals was increased by 18%. Northern blotting showed that the constitutively expressed gene encoding human OPN was maximally stimulated in BSC-1 cells after exposure to COM crystals for 12 hours. Two other calcium-containing crystals, hydroxyapatite and brushite, did not alter OPN gene expression or protein production. OPN mRNA expression was enhanced in canine renal epithelial cells (MDCK line) after exposure to COM crystals for six hours, whereas the constitutive expression of murine OPN mRNA by 3T3 fibroblasts was unchanged. In vivo this glycoprotein could defend the cell against adhesion of crystals in tubular fluid, and/or promote renal interstitial fibrosis in subjects with heavy ciystalluria. Urine is usually supersaturated with calcium and oxalate ions that nucleate to form calcium oxalate crystals [1]. The fate of newly-formed crystals in the nephron is not clear. Once formed a crystal could either grow large enough to occlude the tubule lumen, aggregate with other crystals to form a mass large enough to do so, or adhere to the tubular epithelium; otherwise it would be swept out of the nephron in the flowing fluid within a few minutes. Although growth, aggregation, and cell adhesion may contribute to crystal retention in the nephron, cell-crystal interactions have not been as extensively studied as the former two processes. Crystals of calcium oxalate monohydrate (COM) that form in tubular fluid can bind to the apical surface of cultured renal epithelial cells and become internalized [2-51, thereby stimulating an array of responses including proliferation [6-9]. Cell-crystal interactions in vivo could lead to crystal retention in the kidney and the development of nephrolithiasis, and/or promote interstitial fibrosis and scarring in subjects with excessive crystalluria as occurs in primary hyperoxaluria [8]. We have employed cultures of renal epithelial cells (BSC-i and MDCK lines) and COM crystals as a model system to study the
Word Count: 319 Corresponding Authors: Mary Hammes, DO Associate Professor of Medicine University... more Word Count: 319 Corresponding Authors: Mary Hammes, DO Associate Professor of Medicine University of Chicago 5841 S Maryland Ave., MC-5100 Chicago, IL 60637 [email protected] Phone: 773-702-9892 Fax: 773-753-8301 Anindita Basu, PhD Assistant Professor of Medicine University of Chicago 5841 South Maryland Ave., N417B Chicago, IL 60637 [email protected] Phone: 7738341512 This publication was made possible by the National Institute of Diabetes and Digestive Diseases (NIDDK) and the National Institutes of Health (NIH) under award number RO1DK090769. The study was approved by the Institutional Review Board from the University of Chicago (Protocol number: 11-0269) on August 10, 2011. No conflicts of interest, financial or otherwise, are declared by the author(s). The authors thank all subjects for participation in the study.
International Journal of Nephrology and Kidney Failure, 2017
Background-Vascular access for hemodialysis is best provided by an arteriovenous fistula (AVF). A... more Background-Vascular access for hemodialysis is best provided by an arteriovenous fistula (AVF). AVF fail primarily because of neointimal hyperplasia. Asymmetric dimethlyarginine (ADMA) is a naturally occurring analogue of L-arginine, which is elevated in renal failure and impairs endothelial cell function. ADMA inhibits nitric oxide synthetase, leading to impaired nitric oxide production and contributing to the development of neointimal hyperplasia. ADMA was measured at the time of AVF placement to evaluate associations with access failure. Methods-ADMA was measured at the time of brachiocephalic access placement. Patients were followed for up to 12 months with end-points of access thrombosis or venous stenosis. Results-Sixty patients with primary brachiocephalic fistulas were included in the study cohort. The median value for ADMA drawn at the time of AVF creation was 3.1 µmol/L. ADMA was not significantly associated with early thrombosis or venous stenosis events (P>0.05). Conclusion-Preoperative ADMA levels, as a surrogate for endothelial cell dysfunction and predictor of adverse access event (thrombosis or stenosis), were not associated with subsequent access events Future studies that identify markers of endothelial cell dysfunction are warranted.
The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vas... more The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vascular access. Although a variety of access options are available, the arteriovenous fistula remains the best vascular access. Unfortunately the success rate of mature fistula use remains poor. The creation of an arteriovenous fistula is followed by altered hemodynamic and biological changes that may result in neointimal hyperplasia and eventual venous stenosis. This review provides an overview of these changes and the needed research to provide a long lasting vascular access and hence improve outcomes for patients with end-stage renal disease.
Background. The authors measured urine and blood stone risk factors in African-American (AA) haem... more Background. The authors measured urine and blood stone risk factors in African-American (AA) haemodialysis (HD) patients with new onset of stones during dialysis. Methods. Patients with nephrolithiasis (NL) newly manifested during dialysis were matched by age, sex and urine output and dialysis duration to AA HD patients without history or symptoms of stones. Two 24 h urine and serum samples were collected and analysed for conventional stone risk factors. Results. Three percent of the patients formed new stones while on HD; none had formed stones prior to end-stage renal disease. Newly onset NL patients had higher urine citrate and lower serum potassium levels than HD patients without stones. Conclusion. Usual stone risk factors did not correlate with new stones during dialysis.
... Alternatively Spliced Human Tissue Factor and Thrombotic Tendencies in Hemodialysis Patients ... more ... Alternatively Spliced Human Tissue Factor and Thrombotic Tendencies in Hemodialysis Patients Susan Zawaski1, Mary Hammes2*, Viji Balasubramanian1 ... Plasma asHTF levels were quantified and then compared to a variety of patient parameters collected for each patient. ...
Vascular access maintenance is crucial to providing adequate hemodialysis (HD) and hence preventi... more Vascular access maintenance is crucial to providing adequate hemodialysis (HD) and hence preventing signs and symptoms of uremia. The best vascular assess is a permanent arteriovenous fistula (AVF) because it has the longest survival with the least number of complications. However, because of problems with AVF maturation, the majority of HD in the United States is provided via an arteriovenous graft (AVG) or tunneled cuffed central venous catheter. The most common access complications include infection and thrombosis. For these reasons, a patient is often referred to interventional radiology for a procedure such as a catheter placement, change, or a thrombectomy with angioplasty and/or stent placement. Commonly, a HD patient will present after missing a dialysis session. This might predispose the patient to further complications. This review is intended to provide insight into some of the common medical problems (infectious, hematologic, and cardiac) facing a HD patient as a consequence of uremia. Increased awareness to these medical issues provides guidance to prevent unnecessary complications in this difficult patient population.
High flow arteriovenous fistulas are a common clinical entity affecting patients with end-stage r... more High flow arteriovenous fistulas are a common clinical entity affecting patients with end-stage renal failure receiving hemodialysis. Given the difficulty in predicting who will develop a high flow arteriovenous fistula the exact prevalence is unclear. We present two cases of patients with high flow arteriovenous fistula that developed clinical cardiac failure at a time point after the fistula was placed with findings of significant cephalic arch stenosis. Both patients required treatment of cephalic arch stenosis with balloon angioplasty with subsequent surgical aneurism resection. Accurate and timely diagnosis of high flow arteriovenous hemodynamics by prospective monitoring of volumetric flow and cardiac function is required to halt this process prior to cardiac compromise.
Accurate intravascular volume assessment is critical in the treatment of patients who receive chr... more Accurate intravascular volume assessment is critical in the treatment of patients who receive chronic hemodialysis (HD) therapy. Clinically assessed dry weight is a poor surrogate of intravascular volume; however, ultrasound assessment of the inferior vena cava (IVC) is an effective ...
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