C.K. Abrass, Seattle, Wash. F. Ali, Chicago, Ill. J.R. Asplin, Chicago, Ill. J. Arruda, Chicago, ... more C.K. Abrass, Seattle, Wash. F. Ali, Chicago, Ill. J.R. Asplin, Chicago, Ill. J. Arruda, Chicago, Ill. P. August, New York, N.Y. A.S. Awad, Hershey, Pa. M. Banks, Denver, Colo. V.K. Bansal, Maywood, Ill. E. Benedetti, Chicago, Ill. P. Blake, London, Ontario M. Braun, Houston, Tex. E. Brooks, Chicago, Ill. M. Burnier, Lausanne D. Capone, Naples D.F. Catanzaro, New York, N.Y. J. Cockcroft, Cardiff M. Cooper, Melbourne R. Danziger, Chicago, Ill. J. Daugirdas, Chicago, Ill. S. D’Souza, London, Ontario S. El-Dahr, New Orleans, La. L. Ferder, Ponce, P.R. B.I. Freedman, Winston-Salem, N.C. D. Grekas, Thessaloniki B. Hoppe, Cologne R. Johnson, Aurora, Colo. M. Josephson, Chicago, Ill. K. Kalantar-Zadeh, Orange, Calif. J. Kopp, Bethesda, Md. J.L. Koyner, Chicago, Ill. C.B. Langman, Chicago, Ill. D. Leehey, Hines, Ill. S.L. Linas, Denver, Colo. M.S. Lipkowitz, New York, N.Y. N. Litbarg, Chicago, Ill. P.A. McCullough, Novi, Mich. S. Moe, Indianapolis, Ind. M. Nangaku, Tokyo S.B. Nicholas, Los A...
Background In haemodialysis, maintaining patency of the extracorporeal circuit requires the use o... more Background In haemodialysis, maintaining patency of the extracorporeal circuit requires the use of anticoagulants. Although (low molecular weight) heparins are the mainstay, these are not well tolerated in all patients. Alternative approaches include saline infusion, citrate-containing dialysate, regional citrate anticoagulation or the use of heparin-coated membranes. Asymmetric cellulose triacetate (ATA) dialysers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialysers. The aim of this study was to test the clotting propensity of ATA when used without systemic anticoagulation. Methods We performed a Phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis’ (SAFE) study was a two-arm open-label crossover study. In Arm A, patients were dialysed using 1.9 m2 ATA membranes in combination with a citrate-containing dialysate (1 mM). In Arm B, the ATA mem...
Background Renal osteodystrophy is considered common, but is not well characterized in contempora... more Background Renal osteodystrophy is considered common, but is not well characterized in contemporary kidney transplant recipients. This study reports extensively on bone phenotype by bone histomorphometry, bone densitometry and novel bone biomarkers 1 year after kidney transplantation. Methods A transiliac bone biopsy and dual-energy X-ray absorptiometry scans were performed in 141 unselected kidney transplant recipients in this observational cohort study. Blood and 24-h urine samples were collected simultaneously. Results The median age was 57 ± 11 years, 71% were men and all were of Caucasian ethnicity. Bone turnover was normal in 71% of patients, low in 26% and high in just four cases (3%). Hyperparathyroidism with hypercalcaemia was present in 13% of patients, of which only one had high bone turnover. Delayed bone mineralization was detected in 16% of patients, who were characterized by hyperparathyroidism (137 versus 53 ρg/mL), a higher fractional excretion of phosphate (40 vers...
Journal of the American Society of Nephrology, 2020
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportional... more Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportionally affects frail, elderly patients and those with multiple chronic comorbidities. Whether patients on RRT have an additional risk because of their specific exposure and complex immune dysregulation is controversial. Methods To describe the incidence, characteristics, and outcomes of SARS-CoV-2 infection, we conducted a prospective, multicenter, region-wide registry study in adult patients on RRT versus the general population from March 2 to May 25, 2020. This study comprised all patients undergoing RRT in the Flanders region of Belgium, a country that has been severely affected by coronavirus disease 2019 (COVID-19). Results At the end of the epidemic wave, crude and age-standardized cumulative incidence rates of SARS-CoV-2 infection were 5.3% versus 2.5%, respectively, among 4297 patients on hemodialysis, and 1.4% versus 1.6%, respectively, among 3293 patients with kidney transplants (c...
Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce ... more Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population. Methods We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day. Results Apixaban 5 mg resulted in higher area under the curve (AUC0–48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = ...
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and progno... more Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64,...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2015
CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher... more CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality,...
Pediatric nephrology (Berlin, Germany), Jan 4, 2015
Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization an... more Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization and is an essential player in bone remodeling. Sclerostin is a prototypic soluble canonical Wnt signaling pathway inhibitor that is produced in osteocytes and blocks osteoblast differentiation and function. Therefore, sclerostin is a potent inhibitor of bone formation and mineralization. Accordingly, rodent sclerostin-deficiency models exhibit a strong bone phenotype. Moreover, blocking sclerostin represents a promising treatment perspective against osteoporosis. Beyond the bone field novel data definitely associate Wnt signaling in general and sclerostin in particular with ectopic extraosseous mineralization processes, as is evident in cardiovascular calcification or calciphylaxis. Uremia is characterized by parallel occurrence of disordered bone mineralization and accelerated cardiovascular calcification (chronic kidney disease - mineral and bone disorder, CKD-MBD), linking skeletal and ...
C.K. Abrass, Seattle, Wash. F. Ali, Chicago, Ill. J.R. Asplin, Chicago, Ill. J. Arruda, Chicago, ... more C.K. Abrass, Seattle, Wash. F. Ali, Chicago, Ill. J.R. Asplin, Chicago, Ill. J. Arruda, Chicago, Ill. P. August, New York, N.Y. A.S. Awad, Hershey, Pa. M. Banks, Denver, Colo. V.K. Bansal, Maywood, Ill. E. Benedetti, Chicago, Ill. P. Blake, London, Ontario M. Braun, Houston, Tex. E. Brooks, Chicago, Ill. M. Burnier, Lausanne D. Capone, Naples D.F. Catanzaro, New York, N.Y. J. Cockcroft, Cardiff M. Cooper, Melbourne R. Danziger, Chicago, Ill. J. Daugirdas, Chicago, Ill. S. D’Souza, London, Ontario S. El-Dahr, New Orleans, La. L. Ferder, Ponce, P.R. B.I. Freedman, Winston-Salem, N.C. D. Grekas, Thessaloniki B. Hoppe, Cologne R. Johnson, Aurora, Colo. M. Josephson, Chicago, Ill. K. Kalantar-Zadeh, Orange, Calif. J. Kopp, Bethesda, Md. J.L. Koyner, Chicago, Ill. C.B. Langman, Chicago, Ill. D. Leehey, Hines, Ill. S.L. Linas, Denver, Colo. M.S. Lipkowitz, New York, N.Y. N. Litbarg, Chicago, Ill. P.A. McCullough, Novi, Mich. S. Moe, Indianapolis, Ind. M. Nangaku, Tokyo S.B. Nicholas, Los A...
Background In haemodialysis, maintaining patency of the extracorporeal circuit requires the use o... more Background In haemodialysis, maintaining patency of the extracorporeal circuit requires the use of anticoagulants. Although (low molecular weight) heparins are the mainstay, these are not well tolerated in all patients. Alternative approaches include saline infusion, citrate-containing dialysate, regional citrate anticoagulation or the use of heparin-coated membranes. Asymmetric cellulose triacetate (ATA) dialysers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialysers. The aim of this study was to test the clotting propensity of ATA when used without systemic anticoagulation. Methods We performed a Phase II pilot study in maintenance dialysis patients. The ‘Strategies for Asymmetrical Triacetate dialyzer heparin-Free Effective hemodialysis’ (SAFE) study was a two-arm open-label crossover study. In Arm A, patients were dialysed using 1.9 m2 ATA membranes in combination with a citrate-containing dialysate (1 mM). In Arm B, the ATA mem...
Background Renal osteodystrophy is considered common, but is not well characterized in contempora... more Background Renal osteodystrophy is considered common, but is not well characterized in contemporary kidney transplant recipients. This study reports extensively on bone phenotype by bone histomorphometry, bone densitometry and novel bone biomarkers 1 year after kidney transplantation. Methods A transiliac bone biopsy and dual-energy X-ray absorptiometry scans were performed in 141 unselected kidney transplant recipients in this observational cohort study. Blood and 24-h urine samples were collected simultaneously. Results The median age was 57 ± 11 years, 71% were men and all were of Caucasian ethnicity. Bone turnover was normal in 71% of patients, low in 26% and high in just four cases (3%). Hyperparathyroidism with hypercalcaemia was present in 13% of patients, of which only one had high bone turnover. Delayed bone mineralization was detected in 16% of patients, who were characterized by hyperparathyroidism (137 versus 53 ρg/mL), a higher fractional excretion of phosphate (40 vers...
Journal of the American Society of Nephrology, 2020
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportional... more Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportionally affects frail, elderly patients and those with multiple chronic comorbidities. Whether patients on RRT have an additional risk because of their specific exposure and complex immune dysregulation is controversial. Methods To describe the incidence, characteristics, and outcomes of SARS-CoV-2 infection, we conducted a prospective, multicenter, region-wide registry study in adult patients on RRT versus the general population from March 2 to May 25, 2020. This study comprised all patients undergoing RRT in the Flanders region of Belgium, a country that has been severely affected by coronavirus disease 2019 (COVID-19). Results At the end of the epidemic wave, crude and age-standardized cumulative incidence rates of SARS-CoV-2 infection were 5.3% versus 2.5%, respectively, among 4297 patients on hemodialysis, and 1.4% versus 1.6%, respectively, among 3293 patients with kidney transplants (c...
Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce ... more Background Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population. Methods We conducted a Phase II pharmacokinetics study in which 24 patients on maintenance haemodialysis were given a single dose (2.5 mg or 5 mg) of apixaban, either 30 min before or immediately after dialysis on the mid-week dialysis day. Results Apixaban 5 mg resulted in higher area under the curve (AUC0–48) in comparison with 2.5 mg, although significance could only be reached for dosing pre-dialysis (2.5 mg versus 5 mg, P = 0.008). In line, peak concentrations (Cmax) after dosing pre-dialysis were significantly higher in the 5 mg than in the 2.5 mg groups (P = ...
Journal of the American Society of Nephrology : JASN, Jan 7, 2015
Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and progno... more Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64,...
Clinical journal of the American Society of Nephrology : CJASN, Jan 7, 2015
CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher... more CD14 plays a key role in the innate immunity as pattern-recognition receptor of endotoxin. Higher levels of soluble CD14 (sCD14) are associated with overall mortality in hemodialysis patients. The influence of kidney function on plasma sCD14 levels and its relationship with adverse outcomes in patients with CKD not yet on dialysis is unknown. This study examines the associations between plasma levels of sCD14 and endotoxin with adverse outcomes in patients with CKD. We measured plasma levels of sCD14 and endotoxin in 495 Leuven Mild-to-Moderate CKD Study participants. Mild-to-moderate CKD was defined as presence of kidney damage or eGFR<60 ml/min per 1.73 m(2) for ≥3 months, with exclusion of patients on RRT. Study participants were enrolled between November 2005 and September 2006. Plasma sCD14 was negatively associated with eGFR (ρ=-0.34, P<0.001). During a median follow-up of 54 (interquartile range, 23-58) months, 53 patients died. Plasma sCD14 was predictive of mortality,...
Pediatric nephrology (Berlin, Germany), Jan 4, 2015
Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization an... more Canonical Wnt signaling activity contributes to physiological and adaptive bone mineralization and is an essential player in bone remodeling. Sclerostin is a prototypic soluble canonical Wnt signaling pathway inhibitor that is produced in osteocytes and blocks osteoblast differentiation and function. Therefore, sclerostin is a potent inhibitor of bone formation and mineralization. Accordingly, rodent sclerostin-deficiency models exhibit a strong bone phenotype. Moreover, blocking sclerostin represents a promising treatment perspective against osteoporosis. Beyond the bone field novel data definitely associate Wnt signaling in general and sclerostin in particular with ectopic extraosseous mineralization processes, as is evident in cardiovascular calcification or calciphylaxis. Uremia is characterized by parallel occurrence of disordered bone mineralization and accelerated cardiovascular calcification (chronic kidney disease - mineral and bone disorder, CKD-MBD), linking skeletal and ...
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