Patients/Matériels et méthodes Nous avons réalisé une étude rétrospective sur 118 donneurs durant... more Patients/Matériels et méthodes Nous avons réalisé une étude rétrospective sur 118 donneurs durant une période allant de janvier 1998 à décembre 2016. Le suivi après le don a eu lieu tous les 3 mois la 1 re année, puis tous les ans, avec mesure de la pression artérielle, du débit de filtration glomérulaire (DFG) et de la protéinurie. Observation/Résultats L'âge moyen des donneurs est de 50 ans avec un IMC médian de 25 kg/m 2. Le donneur est le frère ou la soeur dans 50 % des cas, les parents dans 27 % des cas, les époux ou épouses dans 20 % des cas. Avant le don, le DFG moyen est de 100 mL/min, la tension artérielle moyenne à 119/71 mmHg, et la protéinurie aux alentours de 0,04 g/24 h. Le prélèvement est réalisé dans 96 % des cas par néphrectomie à ciel ouvert. Nous ne déplorons aucun décès chez les donneurs en per ou postopératoire. Les complications postopératoires observées sont : les douleurs (69,5 % des cas), l'infection de la paroi (9,3 % des cas), les complications pleuropulmonaires (10,2 % des cas). Une altération transitoire du DFG est notée avec une perte de 33,9 % à 3 mois et de 30,02 % à 1 an. La moitié des donneurs seulement est suivie après le don. Après une moyenne de suivi de 6 ans, le DFG moyen chez 54 donneurs évalués en 2016 est de 73,67 mL/min [44-144 mL/min]. Discussion/Conclusion Un suivi rigoureux des donneurs est impératif. Un registre des donneurs doit être instauré pour pouvoir améliorer le suivi à long terme ce qui permettra une meilleure détermination des facteurs de risque au moment du don. Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.
Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and he... more Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and heart failure. However, acute renal failure (ARF) may occur in patients who are taking these drugs in situations associated with decreased glomerular filtration pressure, such as dehydration caused by acute diarrhea or diuretic therapy. Sixty-four patients who were admitted to the intensive care unit for ARF associated with ACE inhibitor therapy were followed for more than 5 years. In this historical retrospective study, we documented that 45 patients were treated for hypertension (group I) and 19 were treated for heart failure (group II). Their mean age was 71.2 ؎ ؎ 11.6 years. Patients with ARF presented with overt dehydration in 91% and 84% of the cases in groups I and II, respectively. Hypovolemia was caused by diuretics or gastrointestinal fluid loss. Bilateral artery-renal stenosis or stenosis in a solitary kidney was documented in 22% and 10% of patients in groups I and II, respectively. The probability of survival was 91% and 49% at 1 year and 64% and 18% at 5 years, for groups I and II, respectively. Acute renal failure required
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis, 2000
This study investigated the incidence of subclinical abdominal hernia in patients starting perito... more This study investigated the incidence of subclinical abdominal hernia in patients starting peritoneal dialysis (PD). From April 1995 to August 1999, every new patient without clinical evidence of abdominal leakage underwent peritoneal scintigraphy. A total of 59 patients were enrolled in the study. Imaging of the peritoneal cavity was performed by mixing 74 MBq (2 mCi) of 99 m technetium sulfur colloid with 2 L of 1.36% dextrose peritoneal dialysis solution. Sequential gamma camera static images were obtained at 0 minutes, 60 minutes, and after drainage. Ten abdominal hernias (2 diaphragmatic leaks, 8 inguinal hernias) were observed in ten patients (6 males, 4 females; mean age: 65.1 years). One patient with diaphragmatic leak recovered partial renal function and stopped continuous ambulatory peritoneal dialysis (CAPD); the other was switched to automated peritoneal dialysis (APD). Among the eight patients with inguinal hernia, six had no clinical manifestations within eight months ...
prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical pr... more prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical presenta-Background. Carbamylation of proteins by isocyanic acid, the reactive form of cyanate derived from urea, tion of ARF in patients with an unknown medical history of renal disease. is increased in uraemia and may contribute to uraemic toxicity. Kinetics of carbamylation that may reflect uraemic toxicity is not clearly defined in acute renal Keywords: acute renal failure; carbamylation; chronic failure (ARF). renal failure; haemodialysis; uraemia Methods. Twenty-eight patients with ARF and 13 with chronic renal failure (CRF) were included in the study in order to determine changes in carbamylated haemoglobin concentration (CarHb) in ARF. The usefulness Introduction of this parameter for differentiating ARF from CRF was also investigated. CarHb was measured by Carbamylation of haemoglobin (Hb) and other prohigh-performance liquid chromatography after acid teins occurs in uraemia. It results from the nonhydrolysis. enzymatic post-translational modification of proteins Results. Mean CarHb level (expressed as mg carbamyl by isocyanic acid, the reactive form of cyanate derived valine per gram (CV/g) Hb) was significantly higher from the spontaneous dissociation of urea. For Hb, in ARF (54.3±5.2) than in normal subjects the most extensively studied protein in this setting, (31.6±1.3). On admission, CarHb level was correlated cyanic acid reacts with the terminal valine residues with duration of ARF prior to hospitalization in the of both a and b chains. Under physiological conditions, intensive care unit (r2=0.723, P<0.001). CarHb was the level of isocyanate is~1% that of urea [1]. significantly higher at recovery in the subgroup of Carbamylation may contribute to uraemic toxicity. It patients requiring haemodialysis than in the subgroup has been documented that carbamylated proteins are not requiring haemodialysis (82.4±11.3 vs 46.7±5.2, implicated in the atherogenesis of chronic renal failure P<0.01). Similarly dialysis patients lost more weight (CRF) [2,3]. In cultured neuroblastoma cells, car-(8.6±1.4 vs 2.7±0.5 kg, P<0.005) and had higher bamylation of cellular proteins is associated with averaged blood urea levels in the 20 days prior to synthesis of the heat shock protein HSP 72 [4]. recovery (17.6±1.9 vs 11.3±1.8 mol/l, P<0.05). After Carbamylation of lens proteins, such as actin, predisrecovery, CarHb level decreased at a rate of 0.219 mg poses to cataract development [5]. In renal failure, CV/g Hb per day in patients with reversible renal near complete carbamylation of human serum albumin insufficiency. CarHb concentration was higher in (HSA) resulted in a two-third reduction of the binding patients with CRF. A cutoff CarHb value of 100 mg capacity of the protein for small anionic molecules [6 ]. CV/g Hb had a sensitivity of 94% and a positive Carbamylated haemoglobin (CarHb) is the most predictive value of 94% for differentiating ARF from simple, useful and reproductible index for measuring CRF. the carbamylation reaction in vivo. Increased CarHb Conclusions. Kinetics of CarHb showed a near normal levels have been measured in patients with CRF or red blood cell life span in ARF. Changes in CarHb with acute renal failure (ARF). It has been postulated enabled, with a good sensitivity, the distinction to be that CarHb level may reflect the intensity of uraemic made between patients who recovered from ARF and toxicity as has been shown for glycated haemoglobin those with sustained renal impairment, whether due to in the diabetic patient [7,8]. Consequently, CarHb could represent a suitable marker of dialysis adequacy Correspondence and offprint requests to: Professor Jacques Chanard, in chronic haemodialysed patients [9,10]. Since the
Background. Donation after circulatory determination of death (DCDD), formerly non-heart-beating ... more Background. Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been reintroduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. Methods. Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. Results. From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 6 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsyproven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate (Modification of Diet in Renal Disease formula) was 48 6 16 mL/min/1.73m 2 at 1 year and 48 6 15 mL/min/1.73m 2 at the last follow-up. Conclusions. DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.
tral PS was roughly half that of the charged membranes. Filtration of native and glycated  2-mic... more tral PS was roughly half that of the charged membranes. Filtration of native and glycated  2-microglobulin by charged Neutralizing surface electronegativity of the AN69 membrane and neutral dialysis membranes. with PEI did not alter its binding capacity. These results suggest Background. It has been postulated that protein glycation that it would be useful for dialysis protocols to include comparand formation of advanced glycation end products (AGE) are ative studies of both serum native and modified  2 m in order among toxic factors in chronic uremia, whether the renal disto prevent  2 m-amyloidosis. ease is of diabetic or nondiabetic origin. In this setting, AGEmodified  2-microglobulin ( 2 m) may favor dialysis  2 m-related dialysis amyloidosis. Consequently, efficient removal of modified  2 m by highly permeable dialysis membranes is as impor-Chronic renal failure induces the production of various tant as removal of native  2 m to postpone the development of compounds that may have toxic effects [1]. The pathogenic dialysis amyloidosis. role of these compounds in metabolic and structural Methods. To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model changes leading to many disorders, such as dialysis-related was used to test the interactions of native and glycated  2 m with amyloidosis, encountered in long-term hemodialyzed pavarious highly permeable dialysis membranes. An experimental tients is postulated. Recent biochemical and clinical studcircuit with minidialyzers was used. The neutral high-flux polysulies have suggested that modified  2-microglobulin ( 2 m) fone membrane (PS), the electronegative polymethylmetacrylfavors polymerization of the protein and induces amyloid ate membrane (PMMA), the electronegative AN69 membrane and a modified AN69 membrane, the surface of which was neu-deposits [2]. Critical biotransformation of  2 m is associtralized with polyethyleneimine (AN69-PEI), were tested using ated with the serum increase of its main acidic isoform both native  2 m and the more acidic glycated  2 m. Protein with pI 5.1, while the native form has a pI of 5.7. More mass transfer and binding to the membrane were measured. precisely, the acidic isoforms of  2 m, which represent a Results. Mass transfer of glycated  2 m was significantly defew percent of total serum  2 m, in addition to various creased through all membranes tested when compared with native  2 m. This result was due to the increased molecular weight breakdown fragments, contain several  2 adducts due to of  2 m, which became less permeable to porous membranes, oxidation and advanced glycation end products (AGE) whereas adsorption of both native and glycated  2 m to mem-[3-5]. AGEs have been extensively studied and are inbranes, due to ionic interactions, decreased similarly with AN69 creased in patients with diabetes mellitus as well as paand AN69-PEI, but remained unchanged with PS and PMMA. tients with end-stage renal failure not associated with Moreover, surface neutralization of AN69 membrane did not alter its core binding capacity, since  2 m absorption accounted diabetes and in the older population (abstract; Miyata for 98 and 97% and glycated  2 m for 83.7 and 81.4% of the T et al, J Am Soc Nephrol 6:552, 1995) [6-12]. protein removed with AN69 and AN69-PEI, respectively. Removal of  2 m, including AGE-modified  2 m, using Conclusion. Clearance of glycated  2 m through highly perhighly permeable membranes, has been documented meable neutral and negatively charged membranes was lower [13-15]. The constant use of highly permeable synthetic than that of native  2 m, reflecting a decreased sieving coefficient for the neoformed higher molecular weight and confor-dialysis membranes, from dialysis onset in long-term hemomationally altered molecule. The binding capacity of the neudialyzed patients, has been shown to postpone the occurrence of the clinical and radiological expression of juxtaarticular bone and synovial amyloid deposits [16-18].
To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed N... more To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both in...
Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with Hba1c a... more Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with Hba1c assays, but few studies compared directly both parameters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients (16 with acute and two with chronic renal failure, 27 with transplant recipients) as 57.8 ± 22.3 μg carbamylvaline/g Hb (mean ± standard deviation) vs. 31.6 ± 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c was evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II Roche). Whichever the method, mean HbA1c values obtained increased in patients with high (> 60 μg carbamylvaline/g Hb) vs. low (< 45) carbamylated hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not significant. Minor peaks on the chromatograms were however increased in parallel to carbamylated hemoglobin. HbA1c values over 6% were found in 4, 1, 2 and 0 ...
Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acut... more Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acute renal failure (ARF) and cardiovascular instability is the use of acetate in the substitution fluid. Acetate is required to maintain acidity of the polyelectrolytic solution to avoid calcium carbonate precipitation in the presence of bicarbonate. In addition, in patients with cardiovascular instability, acetate metabolism is impaired and further compromises hemodynamics. A new CRRT technique is proposed in which bicarbonate is used as a buffer, but the acetate requirements are cancelled: acetate free veno-venous hemofiltration (AF-CVVH). This technique allows control of acid-base disturbances independent of urea removal. This preliminary report describes the feasibility of the technique based on separate infusion of water and electrolytes administered prefiltration, and isotonic sodium bicarbonate administered post filtration. The setting of the technique, adapted to the PRISMA device (Hospal, Lyon, France), was based on a model predicting the bicarbonate infusion rate for a target plasma bicarbonate level. The AF-CVVH was compared with conventional, continuous veno-venous hemofiltration (CVVH) in a crossover study that showed AF-CVVH allowed fastest control of acidosis, avoiding 70 to 80 mmol/d of acetate transfer to the patient. Urea removal was similar with both techniques. It was concluded that AF-CVVH, when compared with CVVH, has the main advantage of separately controlling urea retention and metabolic acidosis in patients with severe ARF and cardiovascular instability.
The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma c... more The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 microCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled beta2-M excretion by an extrarenal route was nearly nonexistent. The 131I-beta2-M half-life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153+/-33 mg/L of beta2-M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing beta2-M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of 131I-beta2-M binding on the membranes, expressed as beta2-M equivalents, were 0, 16, 54, 58, and 59 mg/m2 for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the beta2-M breakdown and removal in hemodialysis patients. Intact beta2-M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the beta2-M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance beta2-M generation.
In the past few years, alpha-1-microglobulin (a1m) has been copuri®ed from human urine with bikun... more In the past few years, alpha-1-microglobulin (a1m) has been copuri®ed from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have puri®ed a1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was puri®ed with an anti-a1m antibodies CNBr-activated sepharose column. Two molecular species of a1m of respectively 30 and 60 kDa were puri®ed. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-a1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the ®rst test, the presence of a1m of 30 kDa (8 lg/ml) in a medium containing 0.76 mM CaCl 2 (with 45 Ca) and 0.76 mM Ox(NH 4) 2 inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of a1m of 30 kDa in a medium containing 4 mM CaCl 2 and 0.5 mM Na 2 Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modi®cation of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary a1m concentration was signi®cantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 0.29 vs 5.34 1.08 mg/l respectively, P = 0.01). The decreased concentration of a1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.
Clinical Journal of the American Society of Nephrology, 2010
Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation o... more Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis. Eighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed. Initial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m(2). Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m(2). Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation. Our results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.
Patients/Matériels et méthodes Nous avons réalisé une étude rétrospective sur 118 donneurs durant... more Patients/Matériels et méthodes Nous avons réalisé une étude rétrospective sur 118 donneurs durant une période allant de janvier 1998 à décembre 2016. Le suivi après le don a eu lieu tous les 3 mois la 1 re année, puis tous les ans, avec mesure de la pression artérielle, du débit de filtration glomérulaire (DFG) et de la protéinurie. Observation/Résultats L'âge moyen des donneurs est de 50 ans avec un IMC médian de 25 kg/m 2. Le donneur est le frère ou la soeur dans 50 % des cas, les parents dans 27 % des cas, les époux ou épouses dans 20 % des cas. Avant le don, le DFG moyen est de 100 mL/min, la tension artérielle moyenne à 119/71 mmHg, et la protéinurie aux alentours de 0,04 g/24 h. Le prélèvement est réalisé dans 96 % des cas par néphrectomie à ciel ouvert. Nous ne déplorons aucun décès chez les donneurs en per ou postopératoire. Les complications postopératoires observées sont : les douleurs (69,5 % des cas), l'infection de la paroi (9,3 % des cas), les complications pleuropulmonaires (10,2 % des cas). Une altération transitoire du DFG est notée avec une perte de 33,9 % à 3 mois et de 30,02 % à 1 an. La moitié des donneurs seulement est suivie après le don. Après une moyenne de suivi de 6 ans, le DFG moyen chez 54 donneurs évalués en 2016 est de 73,67 mL/min [44-144 mL/min]. Discussion/Conclusion Un suivi rigoureux des donneurs est impératif. Un registre des donneurs doit être instauré pour pouvoir améliorer le suivi à long terme ce qui permettra une meilleure détermination des facteurs de risque au moment du don. Déclaration de liens d'intérêts Les auteurs n'ont pas précisé leurs éventuels liens d'intérêts.
Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and he... more Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and heart failure. However, acute renal failure (ARF) may occur in patients who are taking these drugs in situations associated with decreased glomerular filtration pressure, such as dehydration caused by acute diarrhea or diuretic therapy. Sixty-four patients who were admitted to the intensive care unit for ARF associated with ACE inhibitor therapy were followed for more than 5 years. In this historical retrospective study, we documented that 45 patients were treated for hypertension (group I) and 19 were treated for heart failure (group II). Their mean age was 71.2 ؎ ؎ 11.6 years. Patients with ARF presented with overt dehydration in 91% and 84% of the cases in groups I and II, respectively. Hypovolemia was caused by diuretics or gastrointestinal fluid loss. Bilateral artery-renal stenosis or stenosis in a solitary kidney was documented in 22% and 10% of patients in groups I and II, respectively. The probability of survival was 91% and 49% at 1 year and 64% and 18% at 5 years, for groups I and II, respectively. Acute renal failure required
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis, 2000
This study investigated the incidence of subclinical abdominal hernia in patients starting perito... more This study investigated the incidence of subclinical abdominal hernia in patients starting peritoneal dialysis (PD). From April 1995 to August 1999, every new patient without clinical evidence of abdominal leakage underwent peritoneal scintigraphy. A total of 59 patients were enrolled in the study. Imaging of the peritoneal cavity was performed by mixing 74 MBq (2 mCi) of 99 m technetium sulfur colloid with 2 L of 1.36% dextrose peritoneal dialysis solution. Sequential gamma camera static images were obtained at 0 minutes, 60 minutes, and after drainage. Ten abdominal hernias (2 diaphragmatic leaks, 8 inguinal hernias) were observed in ten patients (6 males, 4 females; mean age: 65.1 years). One patient with diaphragmatic leak recovered partial renal function and stopped continuous ambulatory peritoneal dialysis (CAPD); the other was switched to automated peritoneal dialysis (APD). Among the eight patients with inguinal hernia, six had no clinical manifestations within eight months ...
prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical pr... more prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical presenta-Background. Carbamylation of proteins by isocyanic acid, the reactive form of cyanate derived from urea, tion of ARF in patients with an unknown medical history of renal disease. is increased in uraemia and may contribute to uraemic toxicity. Kinetics of carbamylation that may reflect uraemic toxicity is not clearly defined in acute renal Keywords: acute renal failure; carbamylation; chronic failure (ARF). renal failure; haemodialysis; uraemia Methods. Twenty-eight patients with ARF and 13 with chronic renal failure (CRF) were included in the study in order to determine changes in carbamylated haemoglobin concentration (CarHb) in ARF. The usefulness Introduction of this parameter for differentiating ARF from CRF was also investigated. CarHb was measured by Carbamylation of haemoglobin (Hb) and other prohigh-performance liquid chromatography after acid teins occurs in uraemia. It results from the nonhydrolysis. enzymatic post-translational modification of proteins Results. Mean CarHb level (expressed as mg carbamyl by isocyanic acid, the reactive form of cyanate derived valine per gram (CV/g) Hb) was significantly higher from the spontaneous dissociation of urea. For Hb, in ARF (54.3±5.2) than in normal subjects the most extensively studied protein in this setting, (31.6±1.3). On admission, CarHb level was correlated cyanic acid reacts with the terminal valine residues with duration of ARF prior to hospitalization in the of both a and b chains. Under physiological conditions, intensive care unit (r2=0.723, P<0.001). CarHb was the level of isocyanate is~1% that of urea [1]. significantly higher at recovery in the subgroup of Carbamylation may contribute to uraemic toxicity. It patients requiring haemodialysis than in the subgroup has been documented that carbamylated proteins are not requiring haemodialysis (82.4±11.3 vs 46.7±5.2, implicated in the atherogenesis of chronic renal failure P<0.01). Similarly dialysis patients lost more weight (CRF) [2,3]. In cultured neuroblastoma cells, car-(8.6±1.4 vs 2.7±0.5 kg, P<0.005) and had higher bamylation of cellular proteins is associated with averaged blood urea levels in the 20 days prior to synthesis of the heat shock protein HSP 72 [4]. recovery (17.6±1.9 vs 11.3±1.8 mol/l, P<0.05). After Carbamylation of lens proteins, such as actin, predisrecovery, CarHb level decreased at a rate of 0.219 mg poses to cataract development [5]. In renal failure, CV/g Hb per day in patients with reversible renal near complete carbamylation of human serum albumin insufficiency. CarHb concentration was higher in (HSA) resulted in a two-third reduction of the binding patients with CRF. A cutoff CarHb value of 100 mg capacity of the protein for small anionic molecules [6 ]. CV/g Hb had a sensitivity of 94% and a positive Carbamylated haemoglobin (CarHb) is the most predictive value of 94% for differentiating ARF from simple, useful and reproductible index for measuring CRF. the carbamylation reaction in vivo. Increased CarHb Conclusions. Kinetics of CarHb showed a near normal levels have been measured in patients with CRF or red blood cell life span in ARF. Changes in CarHb with acute renal failure (ARF). It has been postulated enabled, with a good sensitivity, the distinction to be that CarHb level may reflect the intensity of uraemic made between patients who recovered from ARF and toxicity as has been shown for glycated haemoglobin those with sustained renal impairment, whether due to in the diabetic patient [7,8]. Consequently, CarHb could represent a suitable marker of dialysis adequacy Correspondence and offprint requests to: Professor Jacques Chanard, in chronic haemodialysed patients [9,10]. Since the
Background. Donation after circulatory determination of death (DCDD), formerly non-heart-beating ... more Background. Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been reintroduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. Methods. Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. Results. From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 6 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsyproven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate (Modification of Diet in Renal Disease formula) was 48 6 16 mL/min/1.73m 2 at 1 year and 48 6 15 mL/min/1.73m 2 at the last follow-up. Conclusions. DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.
tral PS was roughly half that of the charged membranes. Filtration of native and glycated  2-mic... more tral PS was roughly half that of the charged membranes. Filtration of native and glycated  2-microglobulin by charged Neutralizing surface electronegativity of the AN69 membrane and neutral dialysis membranes. with PEI did not alter its binding capacity. These results suggest Background. It has been postulated that protein glycation that it would be useful for dialysis protocols to include comparand formation of advanced glycation end products (AGE) are ative studies of both serum native and modified  2 m in order among toxic factors in chronic uremia, whether the renal disto prevent  2 m-amyloidosis. ease is of diabetic or nondiabetic origin. In this setting, AGEmodified  2-microglobulin ( 2 m) may favor dialysis  2 m-related dialysis amyloidosis. Consequently, efficient removal of modified  2 m by highly permeable dialysis membranes is as impor-Chronic renal failure induces the production of various tant as removal of native  2 m to postpone the development of compounds that may have toxic effects [1]. The pathogenic dialysis amyloidosis. role of these compounds in metabolic and structural Methods. To define the role of dialysis membrane surface electronegativity on plasma protein transfer, an in vitro model changes leading to many disorders, such as dialysis-related was used to test the interactions of native and glycated  2 m with amyloidosis, encountered in long-term hemodialyzed pavarious highly permeable dialysis membranes. An experimental tients is postulated. Recent biochemical and clinical studcircuit with minidialyzers was used. The neutral high-flux polysulies have suggested that modified  2-microglobulin ( 2 m) fone membrane (PS), the electronegative polymethylmetacrylfavors polymerization of the protein and induces amyloid ate membrane (PMMA), the electronegative AN69 membrane and a modified AN69 membrane, the surface of which was neu-deposits [2]. Critical biotransformation of  2 m is associtralized with polyethyleneimine (AN69-PEI), were tested using ated with the serum increase of its main acidic isoform both native  2 m and the more acidic glycated  2 m. Protein with pI 5.1, while the native form has a pI of 5.7. More mass transfer and binding to the membrane were measured. precisely, the acidic isoforms of  2 m, which represent a Results. Mass transfer of glycated  2 m was significantly defew percent of total serum  2 m, in addition to various creased through all membranes tested when compared with native  2 m. This result was due to the increased molecular weight breakdown fragments, contain several  2 adducts due to of  2 m, which became less permeable to porous membranes, oxidation and advanced glycation end products (AGE) whereas adsorption of both native and glycated  2 m to mem-[3-5]. AGEs have been extensively studied and are inbranes, due to ionic interactions, decreased similarly with AN69 creased in patients with diabetes mellitus as well as paand AN69-PEI, but remained unchanged with PS and PMMA. tients with end-stage renal failure not associated with Moreover, surface neutralization of AN69 membrane did not alter its core binding capacity, since  2 m absorption accounted diabetes and in the older population (abstract; Miyata for 98 and 97% and glycated  2 m for 83.7 and 81.4% of the T et al, J Am Soc Nephrol 6:552, 1995) [6-12]. protein removed with AN69 and AN69-PEI, respectively. Removal of  2 m, including AGE-modified  2 m, using Conclusion. Clearance of glycated  2 m through highly perhighly permeable membranes, has been documented meable neutral and negatively charged membranes was lower [13-15]. The constant use of highly permeable synthetic than that of native  2 m, reflecting a decreased sieving coefficient for the neoformed higher molecular weight and confor-dialysis membranes, from dialysis onset in long-term hemomationally altered molecule. The binding capacity of the neudialyzed patients, has been shown to postpone the occurrence of the clinical and radiological expression of juxtaarticular bone and synovial amyloid deposits [16-18].
To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed N... more To characterize the immune defect of patients with end-stage renal disease (ESRD), we performed NK cell subset analysis in 66 patients with ESRD treated by hemodialysis (n = 59) or peritoneal dialysis (n = 7). Compared with healthy blood donors, patients undergoing chronic dialysis showed a profound decrease in NKG2D+ cells within both the CD8+ T cell (58% vs 67%, p = 0.03) and NK cell (39% vs 56%, p = 0.002) populations. CD56dim cells, which comprise the majority of NK cells in the periphery, were more affected in this regard than were CD56bright cells. Uremic serum could decrease NKG2D expression on NK cells from healthy donors. Among factors that could contribute to the decrease in NKG2D expression in ESRD patients, reactive oxygen species (ROS) play a major role. We found that catalase could reverse the effects of uremic serum on NKG2D expression (p < 0.001) and that ROS down-regulated NKG2D at the mRNA level and at the NK cell surface. Additionally, ESRD patients had both in...
Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with Hba1c a... more Increased carbamylated hemoglobin formed in erythrocytes during uremia may interfere with Hba1c assays, but few studies compared directly both parameters. We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients (16 with acute and two with chronic renal failure, 27 with transplant recipients) as 57.8 ± 22.3 μg carbamylvaline/g Hb (mean ± standard deviation) vs. 31.6 ± 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c was evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2 (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II Roche). Whichever the method, mean HbA1c values obtained increased in patients with high (> 60 μg carbamylvaline/g Hb) vs. low (< 45) carbamylated hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not significant. Minor peaks on the chromatograms were however increased in parallel to carbamylated hemoglobin. HbA1c values over 6% were found in 4, 1, 2 and 0 ...
Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acut... more Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acute renal failure (ARF) and cardiovascular instability is the use of acetate in the substitution fluid. Acetate is required to maintain acidity of the polyelectrolytic solution to avoid calcium carbonate precipitation in the presence of bicarbonate. In addition, in patients with cardiovascular instability, acetate metabolism is impaired and further compromises hemodynamics. A new CRRT technique is proposed in which bicarbonate is used as a buffer, but the acetate requirements are cancelled: acetate free veno-venous hemofiltration (AF-CVVH). This technique allows control of acid-base disturbances independent of urea removal. This preliminary report describes the feasibility of the technique based on separate infusion of water and electrolytes administered prefiltration, and isotonic sodium bicarbonate administered post filtration. The setting of the technique, adapted to the PRISMA device (Hospal, Lyon, France), was based on a model predicting the bicarbonate infusion rate for a target plasma bicarbonate level. The AF-CVVH was compared with conventional, continuous veno-venous hemofiltration (CVVH) in a crossover study that showed AF-CVVH allowed fastest control of acidosis, avoiding 70 to 80 mmol/d of acetate transfer to the patient. Urea removal was similar with both techniques. It was concluded that AF-CVVH, when compared with CVVH, has the main advantage of separately controlling urea retention and metabolic acidosis in patients with severe ARF and cardiovascular instability.
The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma c... more The kinetics of 131I-beta2-microglobulin (beta2-M) were studied using external total body gamma counting in a low noise chamber after administration of trace doses of radioactivity (4 microCi) in 14 uremic patients treated by either hemodialysis or hemofiltration. Data were collected over a 1 week period that included 3 dialysis sessions. The following artificial membranes were used: Cuprophan, polyacrylonitrile AN69, polysulfone, polymethylmethacrylate (PMMA), and polyamide. Radiolabeled beta2-M excretion by an extrarenal route was nearly nonexistent. The 131I-beta2-M half-life was between 2.4 and 8 days, shorter in patients with residual diuresis. A mean removal of 153+/-33 mg/L of beta2-M was obtained per dialysis session with a highly permeable membrane. A hemofiltration session (25 L exchange per session) was slightly more efficient in removing beta2-M than a 4 h hemodialysis session with the same AN69 highly permeable membrane. The amounts of 131I-beta2-M binding on the membranes, expressed as beta2-M equivalents, were 0, 16, 54, 58, and 59 mg/m2 for Cuprophan, polysulfone, polyacrylonitrile AN69, polyamide, and PMMA, respectively. In conclusion, the decrease of total body gamma counting directly reflected the beta2-M breakdown and removal in hemodialysis patients. Intact beta2-M was removed by convection with synthetic, highly permeable membranes. In addition, membrane adsorption accounted for 15% (polysulfone) to near 100% (PMMA) of the beta2-M removal per session. Adsorption was of the same magnitude regardless of the dialysis technique in use, indicating a membrane saturability process. None of the currently available dialysis procedures based on a 3 sessions per week schedule can balance beta2-M generation.
In the past few years, alpha-1-microglobulin (a1m) has been copuri®ed from human urine with bikun... more In the past few years, alpha-1-microglobulin (a1m) has been copuri®ed from human urine with bikunin, a potent inhibitor of calcium oxalate (CaOx) crystallization in vitro. In this study, we have puri®ed a1m without bikunin contamination and investigated its possible role in CaOx crystallization by in vitro and in vivo studies. Alpha-1m was puri®ed with an anti-a1m antibodies CNBr-activated sepharose column. Two molecular species of a1m of respectively 30 and 60 kDa were puri®ed. For each protein, two blots of 30 and 60 kDa cross-reacted with anti-a1m antibodies, suggesting that these two forms were derived one from the other. Both protein species inhibited CaOx crystallization in a dose-dependent manner in two in vitro tests. In the ®rst test, the presence of a1m of 30 kDa (8 lg/ml) in a medium containing 0.76 mM CaCl 2 (with 45 Ca) and 0.76 mM Ox(NH 4) 2 inhibited CaOx crystallization by 38% as estimated by supernatant radioactivity after 1 h of agitation. In the second test, CaOx kinetics were examined for 3 to 10 min in a turbidimetric model at 620 nm. The presence of a1m of 30 kDa in a medium containing 4 mM CaCl 2 and 0.5 mM Na 2 Ox inhibited CaOx crystallization by 41.5%, as estimated by the slope modi®cation of turbidimetric curve. Alpha-1m can be considered as another inhibitor of urinary CaOx crystal formation, as shown by the present in vitro studies. Using an ELISA assay, we found that urinary a1m concentration was signi®cantly lower in 31 CaOx stone formers than in 18 healthy subjects (2.95 0.29 vs 5.34 1.08 mg/l respectively, P = 0.01). The decreased concentration of a1m in CaOx stone formers could be responsible in these patients, at least in part, for an increased risk of CaOx crystalluria.
Clinical Journal of the American Society of Nephrology, 2010
Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation o... more Sarcoidosis is a multisystem disorder of unknown etiology. The outcome of renal transplantation on patients with sarcoidosis is not well known. A few case reports have described recurrence of sarcoidosis after transplant. Here, we report for the first time results and outcome of renal transplantation in a series of patients with sarcoidosis. Eighteen patients with sarcoidosis who underwent renal transplantation were identified retrospectively in eight French renal transplantation departments. Patient medical charts, demographics, and the outcome of renal transplantation were reviewed. Initial renal disease was related to sarcoidosis in 10 patients. At the end of the follow-up (median, 42 months), patient and death-censored graft survival were 94.4% and the mean GFR was 60 ml/min per 1.73 m(2). Five patients (27%) experienced recurrence of sarcoidosis including extra-renal involvement in two patients and renal involvement in three patients. Median GFR was lower in the group of patients with renal recurrence compared with that of the entire cohort: 31 ml/min per 1.73 m(2). Recurrence occurred shortly after transplantation (median period, 13 months). Risk factors for recurrence included primary renal disease related to sarcoidosis and a shorter delay between the last episode of sarcoidosis and renal transplantation. Our results indicate that renal transplantation may be carried out safely in transplant candidates with sarcoidosis. Recurrence is not rare and is likely to affect graft outcome. These results fully justify a specific clinical and histologic monitoring mainly during the early posttransplant period.
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Papers by C. Randoux