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2.
Ther Drug Monit ; 45(5): 637-643, 2023 10 01.
Article in English | MEDLINE | ID: mdl-36750447

ABSTRACT

PURPOSE: Vancomycin dosing remains challenging in patients receiving intermittent hemodialysis, especially in developing countries, where access to therapeutic drug monitoring and model-based dose adjustment services is limited. The objectives of this study were to describe vancomycin population PK in patients receiving hemodialysis in a Malian and French center and examine the optimal loading dose of vancomycin in this setting. METHODS: Population pharmacokinetic analysis was conducted using Pmetrics in 31 Malian and 27 French hemodialysis patients, having a total of 309 vancomycin plasma concentrations. Structural and covariate analyses were based on goodness-of-fit criteria. The final model was used to perform simulations of the vancomycin loading dose, targeting a daily area under the concentration-time curve (AUC) of 400-600 mg.h/L or trough concentration of 15-20 mg/L at 48 hours. RESULTS: After 48 hours of therapy, 68% of Malian and 63% of French patients exhibited a daily AUC of <400. The final model was a 2-compartment model, with hemodialysis influencing vancomycin elimination and age influencing the vancomycin volume distribution. Younger Malian patients exhibited a lower distribution volume than French patients. Dosing simulation suggested that loading doses of 1500, 2000, and 2500 mg would be required to minimize underexposure in patients aged 30, 50, and 70 years, respectively. CONCLUSIONS: In this study, a low AUC was frequently observed in hemodialysis patients in Mali and France after a standard vancomycin loading dose. A larger dose is necessary to achieve the currently recommended AUC target. However, the proposed dosing algorithm requires further clinical evaluation.


Subject(s)
Anti-Bacterial Agents , Vancomycin , Humans , Vancomycin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Renal Dialysis , Computer Simulation , Drug Monitoring , Area Under Curve
3.
Nutrients ; 14(17)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36079711

ABSTRACT

Maintenance hemodialysis induces water-soluble vitamins and trace elements losses, which is why recommendations regarding potential supplementation were provided, but mainly based on conventional hemodialysis. This study's aim was to measure the water-soluble vitamins and trace element losses during one on-line post-dilution hemodiafiltration (HDF) session. Thirty-nine patients under maintenance HDF were enrolled. We used the Theraflux® sampler (Theradial Corp., Orvault, France) to analyze the full session dialysate mass transfer. Blood and dialysate samples were collected before and after one HDF session to measure B1, B2, B6, B9, B12, C vitamins, zinc, and selenium concentrations. Values significantly decreased for B1 (20.2%), B2 (13%), B6 (25.4%), B9 (32.6%), C (66.6%) and selenium (6.7%). No significant differences were found for vitamin B12 and zinc. The dialysate losses per session were 1.12 ± 0.88 mg for vitamin B1, 0.28 ± 0.30 mg for B2, 0.33 ± 0.09 mg for B6, 0.3 ± 0.18 mg for B9, 147.5 ± 145.50 mg for C and 25.75 ± 6.91 mg for zinc. Vitamin B12 and selenium were under detection values. In conclusion, during a standard 4hr-HDF session, we found important losses for vitamin B1, B6, B9, C and zinc, suggesting the need for regular monitoring of plasma levels and systematic supplementation of these compounds.


Subject(s)
Hemodiafiltration , Selenium , Trace Elements , Dialysis Solutions , Humans , Thiamine , Vitamin B 12 , Vitamins , Water , Zinc
4.
Pract Lab Med ; 31: e00296, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35860391

ABSTRACT

Introduction: The aim of the study was to assess the clinical reliability of eGFR values estimated with a creatinine measurement from a point of care (StatSensor®) compared with measured GFR (mGFR) by a gold standard method. Methods: We prospectively included 113 patients undergoing renal function assessment. We compared eGFR using creatinine from capillary blood or venous blood measured by StatSensor® and measured GFR (mGFR) by Passing Bablok regression. Performance of eGFR was estimated by biais, precision and accuracy. Results: A total of 113 subjects were included. Median eGFR values were 59 (10-132), 52 (10-123) and 51 (10-131) ml/min/1.73 m2 for enzymatic, capillary and venous measurements, respectively. There was no difference between P30 and P10 for the three eGFR values (p = 0.11 and p = 0.1 respectively). StatSensor® eGFR tended to be underestimated compared to mGFR. For CKD stage 4/5 patients, concordance was 79 and 84% for eGFR with capillary creatinine and venous creatinine respectively. For mGFR< 60 ml/min/1.73 m2, concordance was 84 and 88% with capillary creatinine and venous creatinine respectively. Conclusion: The use of a handheld blood creatinine monitoring system with eGFR calculation provides a good estimation of GFR and allow to identify patients at high risk of acute kidney injury.

5.
J Am Soc Nephrol ; 33(2): 305-325, 2022 02.
Article in English | MEDLINE | ID: mdl-34607911

ABSTRACT

BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na+-Cl- cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in three families with Gitelman-like electrolyte abnormalities, then investigated 156 families for variants in MT-TI and MT-TF, which encode the transfer RNAs for phenylalanine and isoleucine. Mitochondrial respiratory chain function was assessed in patient fibroblasts. Mitochondrial dysfunction was induced in NCC-expressing HEK293 cells to assess the effect on thiazide-sensitive 22Na+ transport. RESULTS: Genetic investigations revealed four mtDNA variants in 13 families: m.591C>T (n=7), m.616T>C (n=1), m.643A>G (n=1) (all in MT-TF), and m.4291T>C (n=4, in MT-TI). Variants were near homoplasmic in affected individuals. All variants were classified as pathogenic, except for m.643A>G, which was classified as a variant of uncertain significance. Importantly, affected members of six families with an MT-TF variant additionally suffered from progressive chronic kidney disease. Dysfunction of oxidative phosphorylation complex IV and reduced maximal mitochondrial respiratory capacity were found in patient fibroblasts. In vitro pharmacological inhibition of complex IV, mimicking the effect of the mtDNA variants, inhibited NCC phosphorylation and NCC-mediated sodium uptake. CONCLUSION: Pathogenic mtDNA variants in MT-TF and MT-TI can cause a Gitelman-like syndrome. Genetic investigation of mtDNA should be considered in patients with unexplained Gitelman syndrome-like tubulopathies.


Subject(s)
DNA, Mitochondrial/genetics , Gitelman Syndrome/genetics , Mutation , Adolescent , Adult , Aged , Base Sequence , Child , Child, Preschool , Female , Genotype , Gitelman Syndrome/metabolism , Gitelman Syndrome/pathology , HEK293 Cells , Humans , Infant , Kidney/metabolism , Kidney/ultrastructure , Male , Middle Aged , Mitochondria/metabolism , Models, Biological , Nucleic Acid Conformation , Pedigree , Phenotype , Polymorphism, Single Nucleotide , RNA, Transfer, Ile/chemistry , RNA, Transfer, Ile/genetics , RNA, Transfer, Phe/chemistry , RNA, Transfer, Phe/genetics , Solute Carrier Family 12, Member 3/genetics , Young Adult
6.
Nephrol Ther ; 17(4): 252-259, 2021 Aug.
Article in French | MEDLINE | ID: mdl-34034972

ABSTRACT

INTRODUCTION: The health crisis linked to the COVID-19 epidemic has required lockdown measures in France and changes in practices in dialysis centers. The objective was to assess the depressive and anxiety symptoms during lockdown in hemodialysis patients and their caregivers. METHODS: We sent, during lockdown period, between April and May 2020, self-questionnaires to voluntary subjects (patients and caregivers), treated by hemodialysis or who worked in hemodialysis in one of the 14 participating centers in France. We analyzed their perception of dialysis sessions (beneficial or worrying), their stress level (VAS rated from 0 to 10), their anxiety and depressive symptoms (Hospital anxiety and depression scale). Factors associated with stress, anxiety and depression were analyzed with multiple linear regression models. RESULTS: 669 patients and 325 caregivers agreed to participate. 70 % of participants found it beneficial to come to dialysis during confinement. The proportions of subjects with a stress level ≥ 6 linked to the epidemic, confinement, fear of contracting COVID-19 and fear of infecting a loved one were respectively 23.9%, 26.2%, 33.4% and 42%. 39.2% presented with certain (13.7%) or doubtful (19.2%) anxious symptoms. 21.2% presented a certain (7.9%) or doubtful (13.3%) depressive symptomatology. Age, gender, history of psychological disorders and perception of dialysis sessions were associated with levels of stress, anxiety and depression. CONCLUSION: During the lockdown period, in France, the majority of hemodialysis patients and caregivers found it beneficial to come to dialysis. One in three subjects had anxiety symptoms and one in five subjects had depressive symptoms.


Subject(s)
Anxiety/etiology , COVID-19 , Communicable Disease Control , Depression/etiology , Fear , Stress, Psychological/etiology , Age Factors , Aged , Caregivers/psychology , Epidemics , Female , France/epidemiology , Humans , Male , Middle Aged , Sex Factors , Surveys and Questionnaires
7.
Bone ; 138: 115460, 2020 09.
Article in English | MEDLINE | ID: mdl-32485361

ABSTRACT

BACKGROUND AND OBJECTIVES: Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone sections to determine if they are comparable to the standard 7.5 mm samples. DESIGN: We included 68 bone biopsies performed in CKD patients for diagnostic purposes with a 7.5 mm diameter trephine. Quantitative histomorphometric analysis of the whole bone samples was performed including assessment of bone mineralization, turnover and volume. Each histological section (representing the whole 7.5 mm diameter biopsy) was then divided lengthwise in two hemisections (representing the 3.5 mm diameter biopsy). Histomorphometric analysis was repeated this time on the two hemibiopsies for each sample, blinded from initial results. Diagnoses were classified as osteitis fibrosa, adynamic bone disease, mixed uremic bone disease, osteomalacia or other. Correlations between the whole sample and the hemibiopsies for each parameter were studied. Concordance between the various bone parameters and final ROD diagnosis obtained from the whole section versus the two hemi sections was evaluated. RESULTS: Highly significant correlations were found between parameters measured on the whole section and the corresponding hemisections, with r coefficient of 0.98 for osteoid surface and thickness and bone formation rate, 0.97 for osteoclast surface, and 0.96 for bone volume (p < 0.001). Final diagnosis was in full accordance between the whole biopsy and the two corresponding hemi-biopsies in 91% of cases. CONCLUSIONS: Accurate diagnosis of ROD type was obtained by evaluation of bone surface areas of 3 mm diameter. These data suggest that small invasive bone biopsies might provide accurate ROD diagnostics while decreasing both invasiveness and cost of the procedure.


Subject(s)
Bone Diseases , Chronic Kidney Disease-Mineral and Bone Disorder , Osteomalacia , Biopsy , Chronic Kidney Disease-Mineral and Bone Disorder/diagnosis , Humans , Ilium/diagnostic imaging
8.
Nephrol Dial Transplant ; 34(1): 118-122, 2019 01 01.
Article in English | MEDLINE | ID: mdl-29684175

ABSTRACT

Background: Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Methods: Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. Results: The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Conclusion: Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.


Subject(s)
Aminoglycosides/administration & dosage , Anti-Bacterial Agents/administration & dosage , Creatinine/blood , Cystic Fibrosis/drug therapy , Glomerular Filtration Rate/physiology , Kidney/physiology , Lung Transplantation , Adult , Female , Glomerular Filtration Rate/drug effects , Humans , Kidney/drug effects , Kidney Function Tests , Male
9.
J Ren Nutr ; 29(4): 285-288, 2019 07.
Article in English | MEDLINE | ID: mdl-30581063

ABSTRACT

OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥ 18 years, CKD stage 3-5 non dialysis, Sbicar < 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 ± 287 pg/mL, and mean serum Sbicar was 19.3 ± 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 ± 2.9 mmol/L, P < .001) and 4 weeks (23.4 ± 1.9 mmol/L, P < .001). There was no change in serum Klotho at two (630 ± 333 mmol/L) and 4 weeks (632 ± 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 ± 31.6 pg/mmoL), increased by 320% at two weeks (P < .005) and by 280% at 4 weeks (P < .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.


Subject(s)
Dietary Supplements , Glucuronidase/blood , Glucuronidase/urine , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/urine , Sodium Bicarbonate/pharmacology , Acidosis , Aged , Female , Glucuronidase/drug effects , Humans , Klotho Proteins , Male , Middle Aged , Pilot Projects , Prospective Studies , Sodium Bicarbonate/blood , Sodium Bicarbonate/urine
10.
Kidney Int ; 94(5): 983-992, 2018 11.
Article in English | MEDLINE | ID: mdl-30348306

ABSTRACT

Wasting has been associated with increased cardiovascular and all-cause mortality in chronic kidney disease (CKD). We investigated whether serum zinc-alpha2-glycoprotein (ZAG), a potent cachectic and lipid-mobilizing factor that is increased in patients with CKD, predicts clinical outcomes in patients on chronic hemodialysis. We quantified serum ZAG at baseline in a prospective cohort of 252 patients undergoing maintenance hemodialysis. Serum ZAG concentrations were inversely associated with serum albumin, creatinine, and triglycerides and, conversely, positively associated with age. Although ZAG is strongly linked to protein energy wasting (PEW) in patients with cancer, higher ZAG concentrations were not associated with PEW in our cohort. During a mean study follow-up of 954 days, 49 patients died and 62 patients experienced a cardiovascular event. Kaplan-Meier analysis revealed a significant correlation between serum ZAG concentrations and all-cause mortality and cardiovascular events. In separate multivariable Cox regression models, serum ZAG concentrations remained significantly associated with all-cause mortality and cardiovascular events after adjustment for demographic factors (age, sex, and dialysis vintage), metabolic parameters (serum albumin, prealbumin, triglycerides, cholesterol, normalized protein catabolic rate, and body mass index), and cardiovascular risk factors (diabetes, dyslipidemia, history of cardiovascular disease, smoking, and diuretic use as a proxy of residual renal function). Thus, serum ZAG appears to be a strong and independent predictor of mortality and cardiovascular events in patients with end-stage renal disease. Further studies are necessary to confirm this association and to elucidate the underlying mechanisms.


Subject(s)
Renal Dialysis/mortality , Renal Insufficiency, Chronic/blood , Seminal Plasma Proteins/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards Models , ROC Curve , Young Adult , Zn-Alpha-2-Glycoprotein
13.
Pediatr Nephrol ; 33(7): 1165-1172, 2018 07.
Article in English | MEDLINE | ID: mdl-29435659

ABSTRACT

BACKGROUND: Bone impairment appears to be a novel complication of nephropathic cystinosis despite cysteamine therapy. Its exact underlying pathophysiology is nevertheless unclear. The objective of this study was to evaluate bone status among patients included in the French Crystobs study. METHODS: In addition to clinical data, bone status was evaluated using biomarkers (ALP, PTH, 25-D, 1-25D, FGF23), DXA (spine and total body), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius. Results were compared to age- and gender-matched healthy controls (1:2 basis) from the local reference cohorts. RESULTS: At a median age of 22.5 (10.2-34.6) years, 10 patients with nephropathic cystinosis were included (2 receiving conservative therapies, 2 undergoing hemodialysis, 6 with a past of renal transplantation); 7 out of 10 patients complained of a bone symptom (past of fracture, bone deformations, and/or bone pain). Biochemicals and spine DXA did not show any significant abnormalities. Using HR-pQCT, significant decreases in cortical parameters (e.g., cortical thickness 850 (520-1100) versus 1225 (480-1680) µm; p < 0.05) and total volumetric bone mineral density (290 (233-360) versus 323 (232-406) mg/cm3; p < 0.05) were observed in cystinotic patients in comparison to controls at the tibia. There were no differences for trabecular parameters. Similar results were observed at the radius. CONCLUSIONS: In this pilot study, bone impairment (rather cortical than trabecular) is a significant clinical problem in nephropathic cystinosis; 70% of patients displayed significant bone symptoms, during teenage or young adulthood. This new complication should be known by physicians because of its potential dramatic impact on quality of life.


Subject(s)
Bone Density , Bone Diseases/diagnosis , Cortical Bone/physiopathology , Cystinosis/complications , Absorptiometry, Photon , Adolescent , Adult , Age Factors , Biomarkers/analysis , Bone Diseases/epidemiology , Bone Diseases/etiology , Bone Diseases/physiopathology , Child , Cortical Bone/diagnostic imaging , Cysteamine , Cystinosis/drug therapy , Female , Fibroblast Growth Factor-23 , Humans , Male , Pilot Projects , Prevalence , Prospective Studies , Quality of Life , Radius/diagnostic imaging , Radius/physiopathology , Severity of Illness Index , Tibia/diagnostic imaging , Tibia/physiopathology , Tomography, X-Ray Computed , Young Adult
14.
Perit Dial Int ; 37(5): 548-555, 2017.
Article in English | MEDLINE | ID: mdl-28765165

ABSTRACT

BACKGROUND: Bone is known to be impaired in chronic kidney disease and dialysis patients. Recent studies have shown that body composition (fat mass and lean mass) may impact bone health. Some of these effects may be related to mediators that are secreted by adipose tissue. METHODS: The aim of this study was to evaluate the association between body composition (dual x-ray absorptiometry [DEXA]) and adipokines (leptin, adiponectin), with bone density and microarchitecture assessed with high-resolution peripheral quantitative computed tomography (HR-pQCT) in chronic peritoneal dialysis (PD) patients in a single-center prospective study. RESULTS: Twenty-three patients with a median age of 61 years and body mass index (BMI) of 27 kg/m2 were recruited. On univariate analysis, age was negatively associated with total volumetric bone mineral density (vBMD) (r = -0.75, p < 0.01), cortical vBMD (r = -0.85, p < 0.01), and cortical thickness (r = -0.71, p < 0.01). There was a negative association between leptin and cortical thickness (r = -0.48, p = 0.021). Fat mass (FM) was negatively correlated with cortical thickness (r = -0.52, p = 0.012). No association was found between bone parameters and dialysis duration, serum insulin, intact parathyroid hormone, osteocalcin, and adiponectin. The short dialysis vintage could in part explain the lack of correlation with bone parameters. In multivariate analysis, FM was significantly and negatively correlated with total vBMD, cortical and trabecular thickness. CONCLUSIONS: These data suggest that FM is negatively associated with bone quality in PD patients, supporting a relation between body composition and bone that is independent from other dialysis-associated complications. The relative contribution of the different fat deposits (visceral versus subcutaneous) needs to be assessed in future studies.


Subject(s)
Body Composition , Bone Density , Peritoneal Dialysis/adverse effects , Tomography, X-Ray Computed/methods , Absorptiometry, Photon/methods , Adipokines/blood , Aged , Biomarkers/blood , Bone and Bones/physiopathology , Female , Humans , Male , Middle Aged , Prospective Studies
15.
Cancer Chemother Pharmacol ; 79(5): 1043-1049, 2017 May.
Article in English | MEDLINE | ID: mdl-28396940

ABSTRACT

INTRODUCTION: A combined therapy MEK inhibitor, Cobimetinib (CB) and BRAF inhibitor, Vemurafenib (VMF), results in an improvement in progression-free survival among patients with BRAF V600-mutated metastatic melanoma. VMF skin adverse effects attributed to ERK paradoxical activation are decreased by the adjunction of CB. The aim of this study was to determine if this combination also improved the renal side effects of VMF. PATIENTS AND METHODS: To investigate the incidence of acute kidney injury (AKI), we conducted a retrospective observational monocentric study in Lyon Sud University Hospital in France. We included 38 patients with metastatic BRAF-mutated melanomas treated by VMF and CB between March 2015 and June 2016. According to the NCI-CTCAE classification, AKI was defined as an increase in serum creatinine exceeding the baseline concentration by 1.5-fold. Serum creatinine was measured before treatment, then on a monthly basis during treatment, and 1 month after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-), and further subdivided into three groups according to AKI severity (stage 1-5). RESULTS: Of 38 patients, 29 (76%) were AKI-, and all 9 AKI+ patients (24%) were diagnosed within the first trimester of treatment. Three-quarters of AKI (n = 7, 77%) had stage 1 AKI and the remaining 23% stage 2 AKI. Pre-treatment renal function was significantly better in AKI+ group: 105 vs. 80 ml/min/1.73m² AKI-, p = 0.009. Compared to previous results, the AKI incidence under the combined VMF-CB vs. VMF monotherapy was reduced by 60%. CONCLUSION: We reported a reduced incidence and severity of nephrotoxicity of the association inhibitors of BRAF and MEK compared to a BRAF inhibitor monotherapy.


Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Azetidines/administration & dosage , Creatinine/blood , Disease-Free Survival , Enzyme Inhibitors/administration & dosage , Female , Humans , Incidence , Indoles/administration & dosage , Male , Melanoma/complications , Melanoma/genetics , Middle Aged , Piperidines/administration & dosage , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Skin Neoplasms/complications , Skin Neoplasms/genetics , Sulfonamides/administration & dosage , Vemurafenib
16.
Nephrol Dial Transplant ; 32(7): 1217-1223, 2017 Jul 01.
Article in English | MEDLINE | ID: mdl-27342581

ABSTRACT

BACKGROUND: The glycoprotein sclerostin (Scl; 22 kDa), which is involved in bone metabolism, may play a role in vascular calcification in haemodialysis (HD) patients. In the present study, we investigated the relation between serum Scl (sScl) and mortality. The effects of dialysis modality and the magnitude of the convection volume in haemodiafiltration (HDF) on sScl were also investigated. METHODS: In a subset of patients from the CONTRAST study, a randomized controlled trial comparing HDF with HD, sScl was measured at baseline and at intervals of 6, 12, 24 and 36 months. Patients were divided into quartiles, according to their baseline sScl. The relation between time-varying sScl and mortality with a 4-year follow-up period was investigated using crude and adjusted Cox regression models. Linear mixed models were used for longitudinal measurements of sScl. RESULTS: The mean (±standard deviation) age of 396 test subjects was 63.6 (±13.9 years), 61.6% were male and the median follow-up was 2.9 years. Subjects with the highest sScl had a lower mortality risk than those with the lowest concentrations [adjusted hazard ratio 0.51 (95% confidence interval, CI, 0.31-0.86, P = 0.01)]. Stratified models showed a stable sScl in patients treated with HD (Δ +2.9 pmol/L/year, 95% CI -0.5 to +6.3, P = 0.09) and a decreasing concentration in those treated with HDF (Δ -4.5 pmol/L/year, 95% CI -8.0 to -0.9, P = 0.02). The relative change in the latter group was related to the magnitude of the convection volume. CONCLUSIONS: (i) A high sScl is associated with a lower mortality risk in patients with end-stage kidney disease; (ii) treatment with HDF causes sScl to fall; and (iii) the relative decline in patients treated with HDF is dependent on the magnitude of the convection volume.


Subject(s)
Biomarkers/blood , Bone Morphogenetic Proteins/blood , Convection , Hemodiafiltration/adverse effects , Hemodiafiltration/mortality , Kidney Failure, Chronic/mortality , Mortality/trends , Adaptor Proteins, Signal Transducing , Aged , Female , Genetic Markers , Humans , Kidney Failure, Chronic/blood , Kidney Failure, Chronic/therapy , Male , Middle Aged , Prognosis , Survival Rate
17.
Cancer Chemother Pharmacol ; 78(2): 419-26, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27371224

ABSTRACT

PURPOSE: Vemurafenib (VMF) is a B-RAF inhibitor used in the treatment of B-RAF-V600-mutant metastatic melanomas. Reports of acute kidney injury (AKI) in patients treated with VMF are scarce. METHODS: To investigate the incidence and severity of AKI, we conducted a retrospective, observational, monocentric study in the Lyon Sud Hospital University, France, which included 74 patients with metastatic B-RAF-mutated melanomas treated with VMF, between June 2011 and August 2014. According to the Kidney Disease Improving Global Outcomes Guidelines, AKI is defined as an increase in serum creatinine concentration exceeding the baseline concentration by 1.5 fold. Serum creatinine was thus determined before treatment, on a monthly basis during treatment, and 3 months after treatment discontinuation. Patients were divided into two main groups: AKI-positive (AKI+) and AKI-negative (AKI-) and further subdivided into three groups according to AKI severity (stage 1, 2 or 3). To visualize the tissue damage caused by VMF, kidney biopsies were performed for two stage 1 AKI+ patients. RESULTS: Of the 74 patients, 30 (40.5 %) were AKI-, and of the 44 AKI+ patients (59.5 %), 29 (66 %) were diagnosed within the first three months of treatment. There were significantly more men in the AKI+ group: n = 33 (75 %) versus n = 12 (40 %) women, p = 0.004 with an odds ratio for developing AKI of 4.6 (95 % CI 1.48-14.23). Most AKI + cases were considered as stage 1 (n = 40; 91 %) and the remaining four (9 %) as stage 2 AKI. Kidney biopsies revealed interstitial fibrosis and acute focal tubular damage. However, renal failure was reversible in 80 % of patients within 3 months of VMF discontinuation. CONCLUSIONS: We observed frequent, reversible, moderately severe AKI with some histological evidence of tubular and interstitial damage in VMF-treated patients, suggesting that renal function should be carefully monitored in male patients, especially during the first 3 months.


Subject(s)
Acute Kidney Injury/chemically induced , Antineoplastic Agents/adverse effects , Indoles/adverse effects , Melanoma/drug therapy , Sulfonamides/adverse effects , Acute Kidney Injury/epidemiology , Acute Kidney Injury/physiopathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Creatinine/blood , Female , France , Humans , Incidence , Indoles/administration & dosage , Male , Melanoma/genetics , Melanoma/pathology , Middle Aged , Mutation , Neoplasm Metastasis , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Severity of Illness Index , Sulfonamides/administration & dosage , Time Factors , Vemurafenib
19.
J Ren Nutr ; 26(5): 341-5, 2016 09.
Article in English | MEDLINE | ID: mdl-27113628

ABSTRACT

OBJECTIVE: Abnormalities in mineral and bone metabolism are frequent in chronic kidney disease patients. Physical exercise can improve many indicators of physical functioning, and recent studies showed beneficial effects on bone mineral density in the general population. The aim of this study was to evaluate the effects of resistance exercise training on bone markers and body composition in hemodialysis (HD) patients. DESIGN: This was a randomized controlled trial. SUBJECTS: The study included 13 HD patients (46.2% men). INTERVENTION: Patients were divided into a control group and an exercise group, which performed 8 weeks of intradialytic resistance exercise. Serum sclerostin, bone alkaline phosphatase (BAP), insulin, leptin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and body composition were measured before and after the exercise period. RESULTS: In the exercise group, BAP levels increased from 11.4 ± 6.5 to 14.6 ± 6.4 U/L (P < .05) and serum 1,25-dihydroxyvitamin D levels from 46.0 ± 23.5 to 87.2 ± 31.8 ng/mL (P < .05). After exercise, serum BAP levels were inversely correlated with serum sclerostin (r = -0.96, P < .05). There was no change in body composition in either group. CONCLUSION: Resistance exercise training appears to be an interesting approach for stimulating BAP production in HD patients and may prevent bone loss and stimulate bone formation.


Subject(s)
Exercise Therapy , Osteoblasts/physiology , Osteogenesis , Renal Dialysis , Exercise , Health Status , Humans , Male , Pilot Projects , Vitamin D/analogs & derivatives
20.
J Strength Cond Res ; 30(10): 2918-23, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26863587

ABSTRACT

Marinho, SM, Moraes, C, Barbosa, JEdSM, Eduardo, JCC, Fouqe, D, Pelletier, S, and Mafra, D. Exercise training alters the bone mineral density of hemodialysis patients. J Strength Cond Res 30(10): 2918-2923, 2016-Patients with chronic kidney disease undergoing hemodialysis (HD) frequently present low bone mineral density (BMD), and exercise may be useful for treating bone loss. This study aimed to assess the effects of an intradialytic resistance exercise training program (RETP) on BMD in HD patients. Twenty-one patients were enrolled into 2 groups; 10 patients performed exercise (80.0% men; 46.9 ± 12.1 years; 27.0 ± 3.4 kg·m) and 11 patients were in the control group (54.5% men; 50.5 ± 11.5 years; 24.1 ± 8.7 kg·m). Dual-energy x-ray absorptiometry was used to measure the BMD, lean mass, and body fat before and after the supervised RETP (performed with elastic bands and ankle cuffs in both lower limbs 3 times a week for 24 weeks-72 sessions). In the exercise group, 30.0% of patients presented with osteopenia and 20.0% osteoporosis and in the control group, 45.5% osteopenia and 36.4% osteoporosis. Only in the exercise group, the osteoporosis percentage was reduced to 10.0% and the femoral neck BMD and T-score improved from 0.89 ± 0.1 to 0.93 ± 0.1 g·cm and from -1.3 ± 0.8 to -1.0 ± 0.8 g·cm (p ≤ 0.05), respectively, after the intervention. In contrast, these parameters were reduced in the control group. The results suggest that resistance exercise may be useful for improving the BMD in HD patients. In summary, 24 weeks of the supervised RETP played a role in improving the BMD of HD patients.


Subject(s)
Bone Density/physiology , Renal Dialysis , Resistance Training/methods , Absorptiometry, Photon , Adult , Female , Humans , Male , Middle Aged
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