laurence dubourg - Academia.edu (original) (raw)

Papers by laurence dubourg

Journal of the American Society of Nephrology, 2012

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and youn... more The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.

Kidney International, 2019

The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of the ... more The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of the bedside creatinine-based Chronic Kidney Disease in Children (CKiD) equation to estimate glomerular filtration rate (GFR) in children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in adults. However, this approach causes implausible changes in estimated GFR (eGFR) at the transition from pediatric to adult care. We investigated the performance of the KDIGO strategy and various creatinine-based eGFR equations in a crosssectional dataset of 5,764 subjects (age 10-30 years), using directly measured GFR (mGFR) as reference. We also evaluated longitudinal GFR slopes in 136 subjects who transitioned to adult care. Implausible changes in eGFR resulted from the large overestimation (bias= +21 mL/ min/1.73m 2) and poor precision of the CKD-EPI equation in the 18-20 year age group, compared to CKiD in the 16-18 year age group (bias =-2.7 ml_/min/1.73m 2), resulting in a mean change of 23 mL/min/1.73m 2 at the transition to adult care. Averaging the CKiD and CKD-EPI estimates in young adults only partially mitigated this issue. The Full Age Spectrum equation (with and without height), the Lund-Malmö Revised equation, and an age-dependent weighted average of CKiD and CKD-EPI resulted in much smaller changes in eGFR at the transition (change of 0.6,-2.1,-0.9 and-1.8 mL/min/1.73m 2 , respectively). The longitudinal analysis revealed a significant difference in average GFR slope between mGFR and the KDIGO strategy (-2.2 vs. +2.9 mL/min/1.73 m 2 /year), which was not observed with the other approaches. These results suggest that the KDIGO recommendation for GFR estimation at the pediatric-adult care transition should be revisited.

PLOS ONE, 2020

Background Estimating glomerular filtration rate (GFR) is important for clinical management in ki... more Background Estimating glomerular filtration rate (GFR) is important for clinical management in kidney transplantation recipients (KTR). However, very few studies have evaluated the performance of the new GFR estimating equations (Lund-Malmö Revised-LMR, and Full Age Spectrum-FAS) in KTR. Methods GFR was estimated (eGFR) using CKD-EPI, MDRD, LMR, and FAS equations and compared to GFR measurement (mGFR) by reference methods (inuline urinary and iohexol plasma clearance) in 395 deceased-donor KTR without corticosteroids. The equations performance was assessed using bias (mean difference of eGFR and mGFR), precision (standard deviation of the difference), accuracy (concordance correlation coefficient-CCC), and agreements (total deviation index-TDI). The area under receiver operating characteristic curves (ROC) and the likelihood ratio for a positive result were calculated. Results In the total population, the performance of the CKD-EPI, MDRD and FAS equations was significantly lower than the LMR equation regarding the mean [95%CI] difference in bias (

Pediatric Nephrology, 1998

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been i... more The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4±2.2 (±SD) years after chemotherapy (total cumulative dose: methotrexate 41±31 g/m 2 , ifosfamide 39±14 g/m 2 , cisplatin 674±188 mg/m 2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m 2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Pediatric Nephrology, 2008

Nephronophthisis is a chronic tubulointerstitial nephritis with autosomal recessive inheritance w... more Nephronophthisis is a chronic tubulointerstitial nephritis with autosomal recessive inheritance whose evolution to end-stage renal disease is insidious but constant. Fibrous dysplasia of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. We report on a young boy initially diagnosed with fibrous dysplasia of bone, who underwent renal investigation because of treatment with pamidronate. He presented with mild proteinuria (albuminuria/creatininuria 19 mg/mmol) and decreased glomerular filtration rate (GFR) (79 ml/min per 1.73 m 2 body surface area) leading to kidney biopsy, which showed nephronophthisis-like lesions, but neither NPHP1 gene deletion nor UMOD (uromodulin) mutation were identified. No association between fibrous dysplasia of bone and nephronophthisis has yet been described. Nephronophthisis-like nephritis associated with fibrous dysplasia of bone might represent a possible new syndrome in the nephronophthisis and medullary cystic kidney disease complex. However, a fortuitous association between these two conditions is also possible.

Pediatric Nephrology, 2008

Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxi... more Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxicity. Whereas evidence suggests that sodium 2-mercaptoethanesulfonate (mesna) and amifostine protect renal cells against CAA toxicity in vitro, their efficacy in clinical studies is controversial. To better understand the discrepancy between in vivo and in vitro results, we combined the in vivo intraperitoneal administration of either saline or mesna (100 mg/kg) or amifostine (200 mg/kg) in rats and the in vitro study of CAA toxicity to both proximal tubules and precision-cut renal cortical slices. The measured renal cortical concentrations of mesna and amifostine were 0.6±0.1 μmol/g and 1.2±0.2 μmol/g, respectively; these drugs did not cause renal toxicity. Despite this, none of the adverse effects of 0.5 mM CAA was prevented by the previous in vivo administration of mesna or amifostine. Toxicity of 0.5 mM CAA to rat proximal tubules was shown by the fall of cellular adenosine triphosphate (ATP), total glutathione and coenzyme A + acetyl-coenzyme A levels and by the altered metabolic viability of renal cells. Long-term exposure of cortical slices to CAA concentrations ≥30 μM caused severe cell toxicity (i.e. decrease in cellular ATP, total glutathione, and coenzyme A + acetyl-coenzyme A levels), which was not prevented by the in vivo administration of mesna or amifostine.

Hepatology, 2014

Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotop... more Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFRpredicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4-and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score £ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/ min/1.73 m 2). Conclusion: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging.

American Journal of Kidney Diseases, 2008

tient setting has been questioned by some. 4,5 The predominant concern expressed relates to the t... more tient setting has been questioned by some. 4,5 The predominant concern expressed relates to the timing of postbiopsy complications. The majority of complications in our study (83%) occurred within 6 hours of the biopsy. The remainder of patients with complications had hematuria and/or an insignificant hematoma that presented 72 hours after the biopsy. We therefore conclude that outpatient biopsy represents a valuable, safe, and perhaps cost-effective method of obtaining diagnostic renal tissue.

Pediatric Transplantation, 2001

Fading renal hyper®ltration in children following liver transplantation.

Journal of the American Society of Nephrology, 2012

The performance of creatinine-based equations to obtain the estimated GFR in adolescents and youn... more The performance of creatinine-based equations to obtain the estimated GFR in adolescents and young adults is poorly understood. We assessed creatinine-based GFR estimating equations in a cross-section of 751 adolescents and young adults (1054 measurements), using inulin clearance (measured GFR [mGFR]) as the reference method. We evaluated the following: Cockcroft-Gault, four-variable Modified Diet in Renal Disease, and the Chronic Kidney Disease Epidemiology Collaboration equations for adult participants, as well as the Schwartz 2009 and Schwartz-Lyon equations for pediatric age groups. Participants ranged in age from 10 to 26 years (mean 16.8 years); we divided the population into four groups according to age (10-12 years, 13-17 years, 18-21 years, and 21-25 years). Evaluation of the agreement between these formulas and mGFR (e.g., correlation, Bland-Altman plots, bias, and accuracy) showed that there was a good correlation between mGFR and both pediatric formulas in all age groups, whereas the adult formulas substantially overestimated mGFR. In conclusion, we recommend the use of pediatric equations to estimate GFR from childhood to early adulthood.

Kidney International, 2019

The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of the ... more The current Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend the use of the bedside creatinine-based Chronic Kidney Disease in Children (CKiD) equation to estimate glomerular filtration rate (GFR) in children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation in adults. However, this approach causes implausible changes in estimated GFR (eGFR) at the transition from pediatric to adult care. We investigated the performance of the KDIGO strategy and various creatinine-based eGFR equations in a crosssectional dataset of 5,764 subjects (age 10-30 years), using directly measured GFR (mGFR) as reference. We also evaluated longitudinal GFR slopes in 136 subjects who transitioned to adult care. Implausible changes in eGFR resulted from the large overestimation (bias= +21 mL/ min/1.73m 2) and poor precision of the CKD-EPI equation in the 18-20 year age group, compared to CKiD in the 16-18 year age group (bias =-2.7 ml_/min/1.73m 2), resulting in a mean change of 23 mL/min/1.73m 2 at the transition to adult care. Averaging the CKiD and CKD-EPI estimates in young adults only partially mitigated this issue. The Full Age Spectrum equation (with and without height), the Lund-Malmö Revised equation, and an age-dependent weighted average of CKiD and CKD-EPI resulted in much smaller changes in eGFR at the transition (change of 0.6,-2.1,-0.9 and-1.8 mL/min/1.73m 2 , respectively). The longitudinal analysis revealed a significant difference in average GFR slope between mGFR and the KDIGO strategy (-2.2 vs. +2.9 mL/min/1.73 m 2 /year), which was not observed with the other approaches. These results suggest that the KDIGO recommendation for GFR estimation at the pediatric-adult care transition should be revisited.

PLOS ONE, 2020

Background Estimating glomerular filtration rate (GFR) is important for clinical management in ki... more Background Estimating glomerular filtration rate (GFR) is important for clinical management in kidney transplantation recipients (KTR). However, very few studies have evaluated the performance of the new GFR estimating equations (Lund-Malmö Revised-LMR, and Full Age Spectrum-FAS) in KTR. Methods GFR was estimated (eGFR) using CKD-EPI, MDRD, LMR, and FAS equations and compared to GFR measurement (mGFR) by reference methods (inuline urinary and iohexol plasma clearance) in 395 deceased-donor KTR without corticosteroids. The equations performance was assessed using bias (mean difference of eGFR and mGFR), precision (standard deviation of the difference), accuracy (concordance correlation coefficient-CCC), and agreements (total deviation index-TDI). The area under receiver operating characteristic curves (ROC) and the likelihood ratio for a positive result were calculated. Results In the total population, the performance of the CKD-EPI, MDRD and FAS equations was significantly lower than the LMR equation regarding the mean [95%CI] difference in bias (

Pediatric Nephrology, 1998

The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been i... more The acute renal effects of chemotherapy are known, but long-term nephrotoxicity has rarely been investigated. The aim of the present study was to assess long-term renal function in children and adolescents who received at-risk chemotherapy, including cisplatin, ifosfamide, and methotrexate, to treat an osteosarcoma. Renal function tests [creatinine clearance, microalbuminuria, and renal excretion of sodium, potassium, chloride, calcium, magnesium (Mg), phosphorus (P), and uric acid] were prospectively performed 5.4±2.2 (±SD) years after chemotherapy (total cumulative dose: methotrexate 41±31 g/m 2 , ifosfamide 39±14 g/m 2 , cisplatin 674±188 mg/m 2) in 18 children and adolescents. The results were compared with 13 normal volunteers matched for age and sex. Creatinine clearance, which was greater than 80 ml/min per 1.73 m 2 in all patients, correlated with the total dose of ifosfamide (r=0.55, P<0.05) and cisplatin (r=0.48, P<0.05). Microalbuminuria was noted in 4 patients. Hypomagnesemia was present in 4 and hypercalciuria in 3 patients; renal excretion of P, Mg, and uric acid was higher in patients than in controls. Glomerular function was not significantly altered and only mild tubular dysfunction was present. Since renal excretion of P and Mg were increased in patients compared with normal volunteers and hypercalciuria was occasionally seen, divalent ion disorders are the most-likely potential complications.

Pediatric Nephrology, 2008

Nephronophthisis is a chronic tubulointerstitial nephritis with autosomal recessive inheritance w... more Nephronophthisis is a chronic tubulointerstitial nephritis with autosomal recessive inheritance whose evolution to end-stage renal disease is insidious but constant. Fibrous dysplasia of bone is characterized by focal replacement of normal bone and marrow with abnormal bone and fibrous tissue. We report on a young boy initially diagnosed with fibrous dysplasia of bone, who underwent renal investigation because of treatment with pamidronate. He presented with mild proteinuria (albuminuria/creatininuria 19 mg/mmol) and decreased glomerular filtration rate (GFR) (79 ml/min per 1.73 m 2 body surface area) leading to kidney biopsy, which showed nephronophthisis-like lesions, but neither NPHP1 gene deletion nor UMOD (uromodulin) mutation were identified. No association between fibrous dysplasia of bone and nephronophthisis has yet been described. Nephronophthisis-like nephritis associated with fibrous dysplasia of bone might represent a possible new syndrome in the nephronophthisis and medullary cystic kidney disease complex. However, a fortuitous association between these two conditions is also possible.

Pediatric Nephrology, 2008

Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxi... more Chloroacetaldehyde (CAA) is the putative metabolite responsible for ifosfamide-induced nephrotoxicity. Whereas evidence suggests that sodium 2-mercaptoethanesulfonate (mesna) and amifostine protect renal cells against CAA toxicity in vitro, their efficacy in clinical studies is controversial. To better understand the discrepancy between in vivo and in vitro results, we combined the in vivo intraperitoneal administration of either saline or mesna (100 mg/kg) or amifostine (200 mg/kg) in rats and the in vitro study of CAA toxicity to both proximal tubules and precision-cut renal cortical slices. The measured renal cortical concentrations of mesna and amifostine were 0.6±0.1 μmol/g and 1.2±0.2 μmol/g, respectively; these drugs did not cause renal toxicity. Despite this, none of the adverse effects of 0.5 mM CAA was prevented by the previous in vivo administration of mesna or amifostine. Toxicity of 0.5 mM CAA to rat proximal tubules was shown by the fall of cellular adenosine triphosphate (ATP), total glutathione and coenzyme A + acetyl-coenzyme A levels and by the altered metabolic viability of renal cells. Long-term exposure of cortical slices to CAA concentrations ≥30 μM caused severe cell toxicity (i.e. decrease in cellular ATP, total glutathione, and coenzyme A + acetyl-coenzyme A levels), which was not prevented by the in vivo administration of mesna or amifostine.

Hepatology, 2014

Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotop... more Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated. New GFRpredicting equations, based on standardized assays of Pcr and/or CystC, have been recently recommended in the general population but their performance in cirrhosis patients has been rarely studied. We evaluated the performance of the recently published Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI-Pcr, CKD-EPI-CystC, and CKD-EPI-Pcr-CystC) and the more classical ones (4-and 6-variable MDRD and Hoek formulas) in cirrhosis patients referred for renal evaluation before OLT. Inulin clearance was performed in 202 consecutive patients together with the determination of Pcr and CystC with assays traceable to primary reference materials. The performance of the GFR-predicting equations was evaluated according to ascites severity (no, moderate, or refractory) and to hepatic and renal dysfunctions (MELD score £ or >15 and KDOQI stages, respectively). In the whole population, CystC-based equations showed a better performance than Pcr-based ones (lower bias and higher 10% and 30% accuracies). CKD-EPI-CystC equation showed the best performance whatever the ascites severity and in presence of a significant renal dysfunction (GFR <60 mL/ min/1.73 m 2). Conclusion: Pcr-based GFR predicting equations are not reliable in pre-OLT patients even when an IDMS-traceable enzymatic Pcr assay is used. Whenever a CystC-assay traceable to primary reference materials is performed and when a true measurement of GFR is not possible, CystC-based equations, especially CKD-EPI-CystC, may be recommended to evaluate renal function and for KDOQI staging.

American Journal of Kidney Diseases, 2008

tient setting has been questioned by some. 4,5 The predominant concern expressed relates to the t... more tient setting has been questioned by some. 4,5 The predominant concern expressed relates to the timing of postbiopsy complications. The majority of complications in our study (83%) occurred within 6 hours of the biopsy. The remainder of patients with complications had hematuria and/or an insignificant hematoma that presented 72 hours after the biopsy. We therefore conclude that outpatient biopsy represents a valuable, safe, and perhaps cost-effective method of obtaining diagnostic renal tissue.

Pediatric Transplantation, 2001

Fading renal hyper®ltration in children following liver transplantation.