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1.
Contrib Nephrol ; 175: 46-56, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22188687

RESUMO

The process of on-line generation of ultrapure dialysis fluid is a core prerequisite for the safe execution of modern renal replacement therapies such as on-line hemodiafiltration and high-flux hemodialysis. In these extracorporeal treatments with variable degrees of convection, significant volumes of plasma water are removed and replaced with dialysis fluid, which must occur without causing harm to the patient. Historically, on-line generation of sterile and pyrogen-free physiological substitution fluid by the process of membrane ultrafiltration of fresh dialysis fluid has its origin in hemofiltration, a purely convective therapy. Development of this and later therapies is described in the historical context of a successful effort over decades to overcome the above formidable challenge, which was provided jointly by pioneering clinical investigators and a resourceful dialysis industry.


Assuntos
Soluções para Diálise/história , Hemofiltração/métodos , Ultrafiltração/métodos , Hemodiafiltração/métodos , História do Século XX , História do Século XXI , Humanos , Diálise Renal/métodos , Insuficiência Renal/terapia
2.
Nephron Clin Pract ; 112(1): c41-50, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19365139

RESUMO

BACKGROUND/AIMS: The calcimimetic cinacalcet (Mimpara/Sensipar) simultaneously lowers parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) levels in patients with secondary hyperparathyroidism. The OPTIMA study demonstrated that cinacalcet and adjusted doses of vitamin D maximized control of these parameters. This post-hoc analysis of OPTIMA data assessed the impact of reducing or increasing the dose of concomitant vitamin D on PTH, P and Ca in patients receiving cinacalcet. METHODS: Dialysis patients with mean baseline intact PTH (iPTH) 300-800 pg/ml (31.8-84.8 pM) received doses of cinacalcet titrated to achieve an iPTH of 150-300 pg/ml (15.9-31.8 pM). The dose of vitamin D could then be decreased to further reduce serum P or Ca, or increased/initiated to further decrease PTH levels if iPTH >300 pg/ml or to increase Ca if Ca <8.0 mg/dl (2.0 mM). RESULTS: Vitamin D dose was assessed for 345 patients during a 23-week period. A total of 91 and 129 patients had an increase or decrease in vitamin D dose, respectively. By study end, mean iPTH, P, and Ca were similar in both vitamin D groups, although there were differences in biochemical parameters between groups at the start of the study. There were statistically significant reductions from baseline to study end in iPTH and Ca in both groups (p < 0.001). Although P was significantly reduced by week 23 in the group in which vitamin D dose was decreased (p = 0.007), the reduction in P was less and did not achieve significance in the group in which vitamin D dose was increased (p = 0.71). CONCLUSIONS: After initiating cinacalcet, the dose of vitamin D can be adjusted to maximize reductions in PTH, P and Ca; however, vitamin D-induced decreases in PTH need to be balanced with the diminished response in P and Ca.


Assuntos
Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos/uso terapêutico , Vitamina D/administração & dosagem , Adulto , Cálcio/sangue , Cinacalcete , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipercalcemia/tratamento farmacológico , Hipercalcemia/etiologia , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/etiologia , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/etiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Masculino , Hormônio Paratireóideo/sangue , Fósforo/sangue , Diálise Renal , Vitamina D/farmacologia , Vitamina D/uso terapêutico
3.
Clin J Am Soc Nephrol ; 3(1): 36-45, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18178780

RESUMO

BACKGROUND AND OBJECTIVES: Cinacalcet, a novel calcimimetic, targets the calcium-sensing receptor to lower parathyroid hormone (PTH), calcium, and phosphorus levels in dialysis patients with secondary hyperparathyroidism (SHPT). This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional care (vitamin D and phosphate binders) for achieving the stringent National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) targets for dialysis patients. STUDY DESIGN: In this multicenter, open-label study, hemodialysis patients with poorly controlled SHPT were randomized to receive conventional care (n = 184) or a cinacalcet-based regimen (n = 368). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 16-wk dose-optimization phase with the use of algorithms that allowed cinacalcet to be used with adjusted doses of vitamin D. The primary end point was the proportion of patients with mean intact PTH < or =300 pg/ml during a 7-wk efficacy assessment phase. RESULTS: A higher proportion of patients receiving the cinacalcet-based regimen versus conventional care achieved the targets for PTH (71% versus 22%, respectively; P < 0.001), Ca x P (77% versus 58%, respectively; P < 0.001), calcium (76% versus 33%, respectively; P < 0.001), phosphorus (63% versus 50%, respectively; P = 0.002), and PTH and Ca x P (59% versus 16%, respectively, P < 0.001), and allowed a 22% reduction in vitamin D dosage in patients receiving vitamin D at baseline. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 300 to 500 pg/ml) and the cinacalcet dose required was lower in these patients (median = 30 mg/d). CONCLUSIONS: Compared with conventional therapy, a cinacalcet-based treatment algorithm increased achievement of KDOQI treatment targets in dialysis patients in whom conventional therapy was no longer effective in controlling this disease.


Assuntos
Hiperparatireoidismo Secundário/tratamento farmacológico , Falência Renal Crônica/complicações , Naftalenos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Cálcio/sangue , Quelantes/administração & dosagem , Quelantes/efeitos adversos , Cinacalcete , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Masculino , Pessoa de Meia-Idade , Naftalenos/efeitos adversos , Hormônio Paratireóideo/sangue , Fósforo/sangue , Resultado do Tratamento , Vitamina D/administração & dosagem , Vitamina D/efeitos adversos
4.
Nephrol Dial Transplant ; 23(1): 301-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17890745

RESUMO

BACKGROUND: The conversion of patients on stable epoetin therapy to darbepoetin alpha is usually carried out according to the '1 microg darbepoetin =200 U epoetin' rule, which is based on the protein content of the two compounds. Since several observations have suggested that this conversion factor leads to an overestimate of the required darbepoetin dose, the present multicentre study was designed to assess the true conversion ratio by prospectively evaluating the change in darbepoetin alpha dose after conversion from epoetin, which was required to keep haemoglobin (Hb) stable. METHODS: Haemodialysis patients with stable Hb and maintained on either s.c. or i.v. epoetin (alpha or beta) were switched to intravenously administered darbepoetin alpha according to the 1:200 rule. Subjects treated with epoetin two or three times per week received one weekly dose of darbepoetin alpha, subjects on weekly epoetin received darbepoetin alpha every 2 weeks. For 20 weeks, darbepoetin alpha was changed every 2 weeks according to a pre-specified algorithm, if this was needed to keep Hb within +/-1.0 g/dl of each subject's individual baseline. Thereafter, patients entered a 4-week evaluation period. RESULTS: One hundred ad thirty-two patients in 17 Swiss centres were enrolled and 100 completed the study throughout the evaluation period. While mean Hb was maintained stable between baseline and evaluation period (11.8+/-0.6 g/dl in both), the mean required darbepoetin alpha dose decreased from 34.7+/-2.1 to 26.0+/-1.8 microg (-25%, P<0.0001), yielding a mean final conversion ratio of 1:336. A dose decrease was observed in 56 patients, no dose change in 28 and an increase in 16 patients. Dose reduction strongly depended on baseline epoetin dose: no dose reduction was required for baseline epoetin doses <5000 U/week, whereas a 37% lower mean dose was necessary for baseline doses of 7000-10 000 U/week. The darbepoetin alpha dose reduction did not depend on the previous epoetin type (alpha or beta) or the previous epoetin administration route (i.v. vs s.c.). CONCLUSIONS: The mean darbepoetin alpha dose needed to keep Hb stable in patients previously treated with epoetin is significantly lower than the equimolar dose. Although the equimolar 1:200 conversion ratio is appropriate for lower epoetin doses (<5000 IU/week), the darbepoetin dose for patients converting from >or=5000 IU of epoetin per week is more likely to follow a 1:250 to 1:350 conversion rule. If pricing is based on the 1:200 rule such as in Switzerland, this may translate into cost savings.


Assuntos
Eritropoetina/análogos & derivados , Hematínicos/administração & dosagem , Hemoglobinas/análise , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Diálise Renal , Idoso , Darbepoetina alfa , Epoetina alfa , Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Feminino , Humanos , Masculino , Proteínas Recombinantes
5.
Contrib Nephrol ; 158: 161-168, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17684354

RESUMO

Hemodiafiltration (HDF) can augment the efficiency of removal of small and large solutes for renal replacement therapy. Double high-flux HDF was developed in 1984 with the objective to shorten treatment time compared to conventional therapy. It consists of a serial pair of dialyzers in the extracorporeal circuit for optimal diffusion and filtration, with substitution by backfiltration of bicarbonate dialysate under volumetric control. Used in conjunction with high blood and dialysate fl ow rates and high-flux membranes, unmatched high rates of simultaneous diffusive and convective solute transport can be obtained clinically with double HDF. A favorable long-term clinical outcome in comparison with conventional hemodialysis was observed with this therapy, despite shorter treatment times.


Assuntos
Hemodiafiltração/instrumentação , Convecção , Difusão , Desenho de Equipamento , Hemodiafiltração/métodos , Humanos , Cinética , Fatores de Tempo , Resultado do Tratamento
6.
Hemodial Int ; 10(1): 73-81, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16441831

RESUMO

Significant technological changes in blood flow rate, dialyzer membrane permeability, bicarbonate dialysate, and ultrafiltration-controlled delivery systems permitted the implementation of 3 modifications to conventional hemodialysis as follows: high-efficiency hemodialysis (HEHD), high-flux hemodialysis (HFHD), and double-high-flux hemodiafiltration (HDF). The impact of these techniques on the quantity of the treatment administered and treatment time were assessed. One hundred and eighty-three patients were enrolled over 6 years. Monthly Kt/Vurea and dialysis treatment time were compared among the treatment techniques. In vivo extracorporeal clearances were measured for the dialyzers used. In vivo kinetically derived effective dialyzer clearances were calculated from Kt/V. Patient survival and standardized mortality ratio (SMR) were determined for each treatment modality. Treatment time averaged 192+/-28, 176+/-29, and 159+/-32 min, Kt/Vurea averaged 1.33+/-.34, 1.29+/-.30, 1.41+/-.32, and in vivo delivered urea clearance averaged 222+/-51, 272+/-34, and 333+/-43 mL/min for HEHD, HFHD, and HDF, respectively. These results were achieved even in patients with body weights in excess of 80 kgs. Net ultrafiltration rate during the treatment reached 20-30 mL/min, without clinical untoward effects. Blood flow rate ranged between 450-650 mL/min in all patients. Kaplan-Meier Survival analysis yielded a significant difference when high-efficiency treatments were compared with USRDS outcomes. Standardized mortality ratio analysis showed significance for only HDF vs. USRDS. High-efficiency treatments can provide the same quantity of treatment in a shorter period of time without affecting mortality. The increased spectrum of solutes removal provided by HFHD and HDF may be a further advantage of these treatments.


Assuntos
Hemodiafiltração , Diálise Renal , Feminino , Hemodiafiltração/métodos , Humanos , Masculino , Diálise Renal/métodos , Diálise Renal/mortalidade
7.
Nephrol Dial Transplant ; 19(9): 2341-6, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15252154

RESUMO

BACKGROUND: Late referral (LR) to the nephrologist of patients with progressing chronic kidney disease (CKD) has numerous deleterious effects and is observed in many countries. The contributing factors associated with LR are controversial and poorly defined. We hypothesized that these factors might be better identified by analysing patients starting dialysis in three distinct European countries within the same area. METHOD: The referral and progression of kidney failure patterns were analysed with demographic, clinical and biological data in 279 non-selected consecutive patients starting dialysis in eight centres of three adjacent regions in France, Italy and Switzerland. RESULTS: Early referral (>6 months before the start of dialysis) was seen in 200 patients (71.6%), intermediate referral (1-6 months) in 42 (15.1%) and LR (<1 month) in 37 (13.3%). However inter-centre variations were between 2 and 19% for LR and 6-50% for combined late and intermediate referral. There were no differences at the national levels, but LR was more frequent in the large city centres than in the private or regional structures, with 31 out of 169 (18.3%), two out of 55 (5.4%) and four out of 55 (7.3%), respectively, of their patients (P<0.01). By multivariate analysis, it appears that, besides the presence of an active cancer and the CKD progression rate, the centre structure and the referring physician (primary care physicians and nephrologists are less responsible for LR than other medical specialists) play a significant role in the practice of LR. CONCLUSIONS: Within a dialysis cohort spread over adjacent regions of three countries, LR has the same global distribution pattern, indicating that different health and social security systems do not play a major role in inducing or preventing this practice. The contributing factors for LR that were identified are the type of the referring physician and the structure of the dialysis unit. Both factors are potential targets for an educational and collaborative approach.


Assuntos
Diálise/estatística & dados numéricos , Falência Renal Crônica/terapia , Encaminhamento e Consulta/estatística & dados numéricos , Idoso , Estudos de Coortes , Progressão da Doença , Europa (Continente)/epidemiologia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo
8.
J Nephrol ; 17(1): 66-75, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15151261

RESUMO

BACKGROUND: Clinical and therapeutic characteristics of chronic dialysis patients vary widely at national and/or regional levels. Their increased cardiovascular (CV) mortality is not explained by traditional cardiovascular disease (CVD) risk factors only. Therefore, this study aimed to investigate and compare the characteristics of patients starting dialysis in a homogeneous Alpin region and possibly to identify new biological parameters (phenotypes or genotypes), which eould be responsible for the increased CVD seen in end-stage renal disease (ESRD) patients. METHODS: A cohort of 279 non-selected consecutive patients entering a dialysis program was prospectively investigated in eight centers of three adjacent regions in France, Italy and Switzerland. In addition to the usual demographic, clinical and biological data, we analyzed at study entry the blood levels of homocysteine, lipoprotein(a) (Lp(a)) and antioxidized low density lipoprotein (LDL) antibodies, vitamin B12 status, Lp(a) and haptoglobin phenotypes, methylenetetrahydrofolate reductase (MTHFR), angiotensin-converting enzyme (ACE), allele epsilon E4 of apolipoprotein (ApoE4) and plasminogen activator inhibitor-1 (PAI-1) genetic polymorphism. RESULTS: At entry, 90.3% of patients were hypertensive, 30% had type 2 diabetes mellitus and 17.6% were current smokers; 42% of patients had already experienced at least one CV event: peripheral artery disease (26% of the cohort), coronary artery disease (22%) or ischemic cerebro-vascular disease (16%). Forty-two patients had had > or =2 CV events or documented atherosclerotic localizations. Anemia was not optimally treated: mean hemoglobin (Hb) was at 97.7 g/L and, while overall 62% of patients received erythropoietin (EPO) prior to dialysis, large national differences were observed. Compared to the reference population, ESRD patients exhibited increased homocysteinemia, Lp(a) levels and ApoE4 allele prevalence. Conversely, the distribution of Lp(a) phenotype, MTHFR TT, ACE DD and PAI-1 4G/4G was equivalent to that of the reference population. In addition, none of the analyzed phenotypical or genotypical parameters, except for the haptoglobin 2.2 phenotype, could be associated with the existence of a previous adverse CV event. CONCLUSIONS: (1) The clinical characteristics of the ESRD patients entering dialysis in our region were comparable to the currently observed dialysis populations in most European countries with the deleterious role of advancing age, diabetes, previous CVD, smoking and hypertension evident (2). Except for anemia therapy, there were no regional or national differences observed at dialysis start. (3) An analysis of the phenotypic and genotypic CV risk factors demonstrated differences with the reference population only for hyperhomocysteinemia, Lp(a) and ApoE4 allele prevalence, with no notable differences among the participating centers.


Assuntos
Doenças Cardiovasculares/etiologia , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/genética , Estudos de Coortes , Feminino , Genótipo , Haptoglobinas/genética , Homocisteína/sangue , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/genética , Fenótipo , Inibidor 1 de Ativador de Plasminogênio/genética , Polimorfismo Genético , Fatores de Risco
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