Canadian Journal of Kidney Health and Disease, 2021
Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thro... more Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli–induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. Sources of information: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted wi...
Thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different a... more Thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different aetiologies characterized by similar symptoms. The compilation of comprehensive data related to the initial clinical presentation of TMA is challenging due to their rare occurrence. The objective of this study was to assess and determine the predictive value of the clinical presentation of patients with a suspected TMA episode, subsequently confirmed as thrombotic thrombocytopenic purpura (TTP), compared with non-TTP TMA by taking advantage of the centralized ADAMTS-13 testing in Quebec. All ADAMTS-13 activity and antibody titration were performed at CHU Saint-Justine (CHUSJ). Measurements and patient demographics (from April 2012 to December 2019) were extracted from the Laboratory Information System of the CHUSJ. Patients with presumed TMA were classified into TTP when ADAMTS-13 activity was ≤10%, or suspicion of TMA other than TTP (non-TTP TMA) when ADAMTS-13 activity was >10%. Clin...
Clinical Journal of the American Society of Nephrology, 2021
In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat ... more In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopat...
Canadian Journal of Kidney Health and Disease, 2020
Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease... more Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease of uncontrolled activation of the alternative complement pathway that is difficult to diagnose. We have evaluated the Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced. Objective: To evaluate Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced. Methods: The Global aHUS Registry is an observational, noninterventional, multicenter study that has prospectively and retrospectively collected data from patients of all ages with an investigator-made clinical diagnosis of aHUS, irrespective of treatment. Patients of all ages with a clinical diagnosis of aHUS were eligible and invited for enrollment, and those with evidence of Shiga toxin–producing Escherichia c...
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2018
Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy... more Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy of eculizumab. Case series of C3 glomerulopathy. Pediatric and adult patients with C3 glomerulopathy treated with eculizumab between 2010 and 2016 were identified through the C3 glomerulopathy French registry database, and a questionnaire was sent to participating French pediatric and adult nephrology centers, as well as one pediatric referral center in Québec, Canada. Global or partial clinical renal response. Evolution of serum creatinine and proteinuria values. 26 patients (13 children/adolescents) were included. 22 (85%) patients had received steroids, plasma exchange, or immunosuppressive therapy before eculizumab, and 3 of them had rapid progression of their kidney disease despite treatment. At the initiation of eculizumab therapy, 11 (42%) patients had chronic kidney disease, 7 (27%) had rapidly progressive disease, and 3 (12%) required dialysis. After eculizumab treatment (media...
Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in soli... more Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in solid organ transplant recipients. The aims of the present study were to determine the pharmacokinetics of GCV administered intravenously (IV) and orally (p.o.) as pre-emptive anti-CMV therapy in pediatric renal transplant recipients and to monitor trough levels and side-effects during pre-emptive therapy. Eleven pediatric renal transplant recipients (aged 11.0+/-3.9 years) were included. The diagnosis of CMV infection, based on two positive pp-65 CMV blood antigen tests at 1 week apart, was made at 39+/-12 days post renal transplantation. They received IV GCV at a dose of 5.0+/-0.3 mg/kg per 12 h for 15 days, followed by GCV p.o. at a dose of 46.7+/-8.2 mg/kg per 12 h for 3 months. Pharmacokinetics (PK) were studied at steady state and GCV plasma concentrations were measured by high-performance liquid chromatography. After IV GCV administration, PK parameters were: C(0)=0.84+/-0.66 microg/ml; C(max)=11.77+/-2.82 microg/ml; AUC(0-12 h)=42.29+/-17.57 microg/ml per hour; Cl=0.13+/-0.05 l/h per kg. After p.o. GCV administration, PK parameters were: C(0)=1.08+/-0.68 microg/ml; C(max)=2.70+/-1.07 microg/ml; AUC(0-12 h)=18.97+/-9.36 microg/ml per hour; Cl/F=2.97+/-1.42 l/h per kg. Bioavailability (F) was 4.9+/-1.2%. Pre-dose concentrations (C(0)) measured under p.o. GCV (n=51) were 1.29+/-0.80 microg/ml (8 C(0) values were below 0.5 microg/ml). Pp-65 CMV blood antigen tests became negative after 16+/-11 days of treatment. GCV was well tolerated. Because of the limited bioavailability, the recommended high doses of p.o. GCV (50 mg/kg per 12 h) were administered and were associated with trough levels over 0.5 microg/ml. In 1 patient who received an erroneously low dosage p.o., CMV resistance to GCV appeared, requiring foscarnet.
Canadian Journal of Kidney Health and Disease, 2021
Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thro... more Purpose of review: Thrombotic microangiopathy (TMA) is suspected in patients presenting with thrombocytopenia and evidence of a microangiopathic hemolytic anemia. Patients with TMA can be critically ill, so rapid and accurate identification of the underlying etiology is essential. Due to better insights into pathophysiology and causes of TMA, we can now categorize TMAs as thrombotic thrombocytopenic purpura, postinfectious (mainly Shiga toxin-producing Escherichia coli–induced) hemolytic uremic syndrome (HUS), TMA associated with a coexisting condition, or atypical HUS (aHUS). We recognized an unmet need in the medical community to guide the timely and accurate identification of TMA, the selection of tests to clarify its etiology, and the sequence of steps to initiate treatment. Sources of information: Key published studies relevant to the identification, classification, and treatment of TMAs in children or adults. These studies were obtained through literature searches conducted wi...
Thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different a... more Thrombotic microangiopathies (TMA) constitute a group of life-threatening diseases of different aetiologies characterized by similar symptoms. The compilation of comprehensive data related to the initial clinical presentation of TMA is challenging due to their rare occurrence. The objective of this study was to assess and determine the predictive value of the clinical presentation of patients with a suspected TMA episode, subsequently confirmed as thrombotic thrombocytopenic purpura (TTP), compared with non-TTP TMA by taking advantage of the centralized ADAMTS-13 testing in Quebec. All ADAMTS-13 activity and antibody titration were performed at CHU Saint-Justine (CHUSJ). Measurements and patient demographics (from April 2012 to December 2019) were extracted from the Laboratory Information System of the CHUSJ. Patients with presumed TMA were classified into TTP when ADAMTS-13 activity was ≤10%, or suspicion of TMA other than TTP (non-TTP TMA) when ADAMTS-13 activity was >10%. Clin...
Clinical Journal of the American Society of Nephrology, 2021
In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat ... more In the past 20 years, we have witnessed tremendous advances in our ability to diagnose and treat genetic diseases of the kidney caused by complement dysregulation. Staggering progress was realized toward a better understanding of the genetic underpinnings and pathophysiology of many forms of atypical hemolytic uremic syndrome (aHUS) and C3-dominant glomerulopathies that are driven by complement system abnormalities. Many of these seminal discoveries paved the way for the design and characterization of several innovative therapies, some of which have already radically improved patients’ outcomes. This review offers a broad overview of the exciting developments that have occurred in the recent past, with a particular focus on single-gene (or Mendelian), complement-driven aHUS and C3-dominant glomerulopathies that should be of interest to both nephrologists and kidney researchers. The discussion is restricted to genes with robust associations with both aHUS and C3-dominant glomerulopat...
Canadian Journal of Kidney Health and Disease, 2020
Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease... more Background: Atypical hemolytic uremic syndrome (aHUS) is an extremely rare, heterogeneous disease of uncontrolled activation of the alternative complement pathway that is difficult to diagnose. We have evaluated the Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced. Objective: To evaluate Canadian patients enrolled in the Global aHUS Registry to provide a Canadian perspective regarding the diagnosis and management of aHUS and the specific challenges faced. Methods: The Global aHUS Registry is an observational, noninterventional, multicenter study that has prospectively and retrospectively collected data from patients of all ages with an investigator-made clinical diagnosis of aHUS, irrespective of treatment. Patients of all ages with a clinical diagnosis of aHUS were eligible and invited for enrollment, and those with evidence of Shiga toxin–producing Escherichia c...
American journal of kidney diseases : the official journal of the National Kidney Foundation, 2018
Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy... more Cases reports and small series of patients with C3 glomerulopathy have reported variable efficacy of eculizumab. Case series of C3 glomerulopathy. Pediatric and adult patients with C3 glomerulopathy treated with eculizumab between 2010 and 2016 were identified through the C3 glomerulopathy French registry database, and a questionnaire was sent to participating French pediatric and adult nephrology centers, as well as one pediatric referral center in Québec, Canada. Global or partial clinical renal response. Evolution of serum creatinine and proteinuria values. 26 patients (13 children/adolescents) were included. 22 (85%) patients had received steroids, plasma exchange, or immunosuppressive therapy before eculizumab, and 3 of them had rapid progression of their kidney disease despite treatment. At the initiation of eculizumab therapy, 11 (42%) patients had chronic kidney disease, 7 (27%) had rapidly progressive disease, and 3 (12%) required dialysis. After eculizumab treatment (media...
Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in soli... more Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in solid organ transplant recipients. The aims of the present study were to determine the pharmacokinetics of GCV administered intravenously (IV) and orally (p.o.) as pre-emptive anti-CMV therapy in pediatric renal transplant recipients and to monitor trough levels and side-effects during pre-emptive therapy. Eleven pediatric renal transplant recipients (aged 11.0+/-3.9 years) were included. The diagnosis of CMV infection, based on two positive pp-65 CMV blood antigen tests at 1 week apart, was made at 39+/-12 days post renal transplantation. They received IV GCV at a dose of 5.0+/-0.3 mg/kg per 12 h for 15 days, followed by GCV p.o. at a dose of 46.7+/-8.2 mg/kg per 12 h for 3 months. Pharmacokinetics (PK) were studied at steady state and GCV plasma concentrations were measured by high-performance liquid chromatography. After IV GCV administration, PK parameters were: C(0)=0.84+/-0.66 microg/ml; C(max)=11.77+/-2.82 microg/ml; AUC(0-12 h)=42.29+/-17.57 microg/ml per hour; Cl=0.13+/-0.05 l/h per kg. After p.o. GCV administration, PK parameters were: C(0)=1.08+/-0.68 microg/ml; C(max)=2.70+/-1.07 microg/ml; AUC(0-12 h)=18.97+/-9.36 microg/ml per hour; Cl/F=2.97+/-1.42 l/h per kg. Bioavailability (F) was 4.9+/-1.2%. Pre-dose concentrations (C(0)) measured under p.o. GCV (n=51) were 1.29+/-0.80 microg/ml (8 C(0) values were below 0.5 microg/ml). Pp-65 CMV blood antigen tests became negative after 16+/-11 days of treatment. GCV was well tolerated. Because of the limited bioavailability, the recommended high doses of p.o. GCV (50 mg/kg per 12 h) were administered and were associated with trough levels over 0.5 microg/ml. In 1 patient who received an erroneously low dosage p.o., CMV resistance to GCV appeared, requiring foscarnet.
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