RESUMEN
Gout affects 15%-30% of individuals with advanced kidney disease. Allopurinol which is rapidly and extensively metabolised to an active metabolite, oxypurinol, is the most commonly prescribed urate-lowering therapy. Oxypurinol is almost entirely eliminated by the kidneys (>95%) and has an elimination half-life of 18-30 h in those with normal kidney function. However, oxypurinol pharmacokinetics are poorly understood in individuals with kidney failure on peritoneal dialysis. This study characterised the elimination of oxypurinol and urate in people with gout receiving peritoneal dialysis. Oxypurinol steady-state oral clearance (CL/F), elimination half-life as well as kidney (CLk) and peritoneal (CLpd) clearances for oxypurinol and urate were calculated from the plasma, urine and dialysate concentration data for each individual. Our results demonstrate that oxypurinol and urate are removed by peritoneal dialysis, accounting for more than 50% of oxypurinol and urate clearances. An allopurinol dose about 50%-60% lower than the usual dose used for a patient with normal kidney function will provide adequate urate-lowering therapy.
Asunto(s)
Supresores de la Gota , Gota , Oxipurinol , Diálisis Peritoneal , Ácido Úrico , Humanos , Ácido Úrico/sangre , Gota/tratamiento farmacológico , Gota/sangre , Masculino , Oxipurinol/farmacocinética , Supresores de la Gota/farmacocinética , Supresores de la Gota/uso terapéutico , Persona de Mediana Edad , Femenino , Anciano , Alopurinol/uso terapéutico , Alopurinol/farmacocinética , Eliminación Renal , Semivida , Soluciones para Diálisis/farmacocinéticaRESUMEN
BACKGROUND: While assessment of membrane characteristics is fundamental to peritoneal dialysis (PD) prescription in patients initiating therapy, peritoneal equilibration test has theoretical and practical drawbacks. We wished to determine whether an equation using simple clinical variables could predict fast (above population mean) peritoneal solute transfer rate without dialysate sampling. METHODS: We measured peritoneal solute transfer rate, as determined by peritoneal equilibration test using the 4-h dialysate to plasma creatinine ratio, in consecutive PD outpatients attending a single tertiary hospital for their first clinical follow-up within 3 months of dialysis initiation. An equation estimating peritoneal solute transfer rate based on readily available clinical variables was generated in a randomly selected modeling group and tested in a distinct validation group. RESULTS: We included 712 patients, with 562 in the modeling group and 150 in the validation group. Mean age was 58.4 ± 15.9 with 431 (60.5%) men. Mean peritoneal solute transfer rate value was 0.73 ± 0.13. An equation based on gender, race, serum sodium and albumin yielded a receiving operator characteristics (ROC) area under the curve (AUC) to detect fast peritoneal solute transfer rate (> 0.73) of 0.74 (0.67-0.82). Estimated peritoneal solute transfer rate values based on percentiles 15th (> 0.66), 20th (> 0.68), 25th (> 0.69) and 30th (> 0.70) could rule out fast peritoneal solute transfer rate with negative predictive values of 100%, 93.5%, 84.2% and 80.0%, respectively. CONCLUSIONS: An equation based on simple clinical variables allows ruling out fast transport in a significant proportion of patients initiating PD with a high degree of confidence without requiring dialysate sampling. This could prove useful in guiding dialysis prescription of PD patients in daily clinical practice, particularly in low-resource settings.
Asunto(s)
Creatinina , Soluciones para Diálisis , Diálisis Peritoneal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Soluciones para Diálisis/farmacocinética , Creatinina/sangre , Adulto , Peritoneo/metabolismo , Valor Predictivo de las Pruebas , Sodio/sangre , Sodio/análisis , Área Bajo la Curva , Curva ROC , Factores de Tiempo , Transporte Biológico , Modelos Biológicos , Biomarcadores/sangre , Albúmina Sérica/metabolismo , Albúmina Sérica/análisis , Fallo Renal Crónico/terapia , Fallo Renal Crónico/sangre , Reproducibilidad de los ResultadosRESUMEN
Peritoneal equilibration test (PET) is the gold standard for evaluating peritoneal transport, and measurement of the drain volume after 4-h dwell time with glucose 4.25% is a simple means of evaluating failure of ultrafiltration. The study objective was to verify if the measurement of the volume drained after 4 h dwell of icodextrin at 7.5% (ICO), has a better correlation with the parameters of PET. Patients in a peritoneal dialysis program (N = 35) underwent three procedures: PET; determination of the drain volume after a 4-h dwell with glucose 4.25%; and determination of the drain volume after a 4-h dwell with ICO. Among patients who were classified as high transporters, the ultrafiltration volume was greater after ICO use. The ICO ultrafiltration volume correlated negatively with the ratio between the 4- and 0-h dialysate glucose concentrations (D4/D0 ratio, r = -0.579; P = 0.002), correlating positively with the dialysate-to-plasma ratio for creatinine (D/PCr ratio, r = 0.474; P = 0.002). For ICO, the area under the receiver operating characteristic curve was 0.867 and 0.792 for the D/PCr and D4/D0 ratios (P < 0.0001 and P = 0.004, respectively), compared with 0.738 and 0.710 for glucose 4.25% (P = 0.020 and P = 0.041, respectively). A cut-off volume of 141 mL discriminated high/high-average transporters from low/low-average transporters. Volume drained after ICO use better predicts peritoneal transport patterns than does that drained after the use of glucose 4.25%.
Asunto(s)
Soluciones para Diálisis/farmacocinética , Icodextrina/farmacocinética , Diálisis Peritoneal , Peritoneo/fisiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The majority of peritoneal dialysates use glucose to generate an osmotic gradient for the convective removal of water and Na. Although glucose can potentially be absorbed, previous studies have failed to establish whether this leads to increased fat weight gain. We measured body composition using bioimpedance in peritoneal dialysis (PD) patients, electively starting PD, attending for their first assessment of peritoneal membrane function after 2-3 months, and then after 12 months. We studied 143 patients: eighty-nine (62·2 %) males, fifty-three (37·1 %) diabetics, mean age 61·3 (SD 14·9) years, with ninety (62·1 %) patients treated by automated PD cyclers with a daytime icodextrin exchange and thirty-seven (25·9 %) by continuous ambulatory PD. Median fat mass increased by 1·8 (-0·5 to 4·1) kg, whereas fat-free mass fell -1·3 (-2·9 to 1·0) kg, and the increase in fat mass was negatively associated with the fall in soft lean mass (r -0·41, P < 0·001). Increased fat mass was associated with measured peritoneal glucose absorption (r 0·69, P < 0·001), and glucose absorption was associated with the amount of 22·7 g/l glucose dialysate (OR 2·0, 95 % CI 1·5, 2·5, P < 0·001), peritoneal urea clearance (OR 9·5, 95 % CI 2·4, 37·1, P = 0·001) and male sex (OR 4·8, 95 % CI 1·5, 14·9, P = 0·008). We report an observational study in prevalent PD patients following body composition from their first assessment of PD membrane function for approximately 12 months, and despite the majority of patients prescribed icodextrin, we have demonstrated not only an association between intra-peritoneal glucose absorption and fat weight gain but also loss of fat-free mass.
Asunto(s)
Composición Corporal/efectos de los fármacos , Glucosa/farmacocinética , Absorción Peritoneal/efectos de los fármacos , Diálisis Peritoneal/efectos adversos , Aumento de Peso/efectos de los fármacos , Tejido Adiposo/metabolismo , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/terapia , Soluciones para Diálisis/farmacocinética , Impedancia Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND AND AIMS: Glucose-containing peritoneal dialysates are used to generate an osmotic gradient for the convective removal of water and sodium. Predictive equations were developed to estimate glucose absorption without having to formally measure changes in dialysate glucose. In view of the changes in peritoneal dialysis prescriptions over time, we compared predicted and measured glucose absorption. SUBJECTS/METHODS: We measured peritoneal glucose losses when peritoneal dialysis patients attended their first assessment of peritoneal membrane function, and compared this to glucose exposure and Kidney Disease Outcomes Quality Initiative, Grodstein and Bodnar predictive equations. RESULTS: We studied 689 patients; 329 (56.9%) males, 53 (37.1%) diabetics, with mean age 57.1 ± 16.2 years, with 186 treated by automated peritoneal dialysis cyclers and 377 by automated peritoneal dialysis with a daytime icodextrin exchange and 126 by continuous ambulatory peritoneal dialysis. Using Bland -Altman analysis, all equations demonstrated systematic bias overestimating glucose absorption with increasing glucose absorption. For continuous ambulatory peritoneal dialysis patients, the Kidney Disease Outcomes Quality Initiative formula underestimated glucose absorption (bias 188 (-39 to 437) mmol/day, as did Grodstein (bias 37.9 (-105 to 29) mmol/day, whereas mean bias for Bodnar was -29 (-130 to 180)). There was systematic overestimation for all equations for both automated peritoneal dialysis with and without a daytime exchange, with increasing bias with greater glucose absorption. CONCLUSION: Although formally measuring peritoneal glucose absorption is time consuming and requires patient co-operation, current predictive equations overestimate glucose absorption and do not provide accurate estimations of glucose absorption particularly for automated peritoneal dialysis patients.
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Soluciones para Diálisis/farmacocinética , Glucosa/farmacocinética , Icodextrina/farmacocinética , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Diálisis Peritoneal Ambulatoria Continua , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peritoneo/metabolismo , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Peritoneal dialysis (PD) is an optimal renal replacement therapy for patients while waiting for kidney transplantation, but functional failure of the peritoneal membrane (PM), mainly induced by exposure to PD solutions, force many patients to early abandon PD therapy. PM function is evaluated by the peritoneal equilibration test (PET), a tedious technique only detecting alterations in extensively damaged PM. In a previous study, we showed that peritoneal dialysis effluent contained extracellular vesicles (PDE-EV), and that their proteome was significantly different between newly enrolled and long-term PD patients. Here, we report the results of a longitudinal study and compare PDE-EV proteome changes with PET results. METHODS: PDE was collected from 11 patients every 6 months (coincident with PET controls) from 0 months up to 24 months on PD. PDE-EV were isolated by size-exclusion chromatography and the proteome was analyzed by mass spectrometry (LC-MS/MS). Bioinformatic analyses were conducted to evaluate differences between groups. RESULTS: At follow-up endpoint, patients were classified as Stable (n = 7) or Unstable (n = 4) according to PET evolution. Strikingly, PDE-EV from the Stable group showed a significantly higher protein expression compared to Unstable patients already at 6 months on PD, when PET alterations had not been detected yet. CONCLUSIONS: PDE-EV proteome show alterations much earlier than PET monitoring, thus unveiling the potential of PDE-EV proteins as feasible biomarkers of PM alteration in PD patients.
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Soluciones para Diálisis/farmacocinética , Vesículas Extracelulares/metabolismo , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Proteómica/métodos , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Cromatografía Liquida , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Humanos , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Peritoneo/metabolismo , Espectrometría de Masas en Tándem , Factores de TiempoRESUMEN
Dialysis adequacy is an independent predictor of high mortality rates in hemodialysis patients. Intradialytic exercise is a potential strategy to increase uremic solute removal by increasing blood flow to low perfusion tissue beds. The purpose of this review is to establish the efficacy of intradialytic exercise for hemodialysis adequacy. Additionally, this review aims to provide practical information to aid health care professionals implement intradialytic exercise for dialysis adequacy. Database and hand searches identified 15 published interventional studies that implemented intradialytic exercise for dialysis adequacy as a primary outcome measure in adult maintenance hemodialysis patients. Data pertaining to dialytic solute clearance of urea, creatinine, beta2 microglobulin, phosphate, and potassium were extracted. Mean differences, normalized to percentages, and effect sizes were calculated and reported. The current data pertaining to the use of intradialytic exercise for improving dialysis adequacy in terms of Kt/Vurea or small molecule uremic toxin clearance are equivocal. Limited data showed that intradialytic exercise has no effect middle molecule toxin (beta2 - microglobulin) clearance. Intradialytic exercise favored increased phosphate removal showing medium to large effects for reduced serum concentrations, reduced rebound and increased clearance. In summary, supervised light to moderate intradialytic aerobic cycling appears to be beneficial for increasing phosphate removal and may be an adjunct therapy for patients failing to meet clinical phosphate targets. Further work is required to establish the effect of intradialytic exercise on Kt/Vurea and other middle molecule and protein bound solutes. Research aimed at establishing the most effective exercise prescription for improved solute clearance is warranted.
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Soluciones para Diálisis/farmacocinética , Terapia por Ejercicio/métodos , Fallo Renal Crónico/terapia , Calidad de Vida , Diálisis Renal/métodos , Uremia/prevención & control , Anciano , Terapia Combinada , Creatinina/sangre , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/diagnóstico , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Resultado del Tratamiento , Urea/sangreRESUMEN
BACKGROUND: The kinetics of ß2-microglobulin during hemodialysis and hemodiafiltration is well described by a two-compartment model where clearance by the dialyzer is from a central compartment volume that approximates plasma volume and a total distribution volume that approximates extracellular fluid volume. The kinetics of middle molecules with molecular weights larger than ß2-microglobulin have not been extensively studied. METHODS: Intradialytic plasma concentrations and overall dialyzer clearances of ß2-microglobulin (11.8 kD), myoglobin (16.7 kD) and complement factor D (24.4 kD) were used to estimate three kinetic parameters from a two-compartment model, namely intercompartmental clearance, central compartment volume and total distribution volume, in hemodialysis patients; these data were collected during two clinical trials of medium cut-off dialyzers (with extended middle molecule removal) during hemodialysis and high-flux dialyzers during hemodialysis and hemodiafiltration. In the current exploratory analyses, the kinetic parameters from all dialyzers were combined. Overall dialyzer clearance was evaluated by total mass removed in the dialysate. RESULTS: In total, 345 sets of kinetic parameters from 35 patients were determined. Intercompartmental clearance and central compartment volume for myoglobin and complement factor D were smaller (P < 0.001) than those for ß2-microglobulin. Independent of middle molecule, intercompartmental clearance and central compartment volume were associated with overall dialyzer clearance (P < 0.001), but total distribution volume was not (P = 0.083). CONCLUSIONS: A two-compartment kinetic model can only describe intradialytic kinetics of middle molecules with molecular weights larger than ß2-microglobulin if the central compartment is small and dependent on overall dialyzer clearance.
Asunto(s)
Soluciones para Diálisis/farmacocinética , Diálisis Renal/métodos , Uremia/terapia , Microglobulina beta-2/metabolismo , Biomarcadores/metabolismo , Factor D del Complemento/metabolismo , Estudios Cruzados , Hemodiafiltración/métodos , Humanos , Estudios Prospectivos , Uremia/metabolismoRESUMEN
BACKGROUND: Ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overall peritoneal transport characteristics in UFF patients in relation to corresponding local alterations of peritoneal tissue and capillary wall transport properties. METHODS: Six-hour dwell studies using 3.86% glucose solutions and radioisotopically labelled serum albumin added to dialysate as a volume marker were analysed in 31 continuous ambulatory PD patients, 20 with normal ultrafiltration (NUF) and 11 with UFF. For each patient, the physiologically based parameters were evaluated for both transport barriers using the spatially distributed approach based on the individual intraperitoneal profiles of volume and concentrations of glucose, sodium, urea and creatinine. RESULTS: UFF patients as compared with NUF patients had increased solute diffusivity in both barriers, peritoneal tissue and capillary wall, decreased tissue hydraulic conductivity and increased local lymphatic absorption and functional decrease in the fraction of the ultra-small pores. This resulted in altered distribution of fluid and solutes in the peritoneal tissue, and decreased penetration depths of fluid and solutes into the tissue in UFF patients. CONCLUSIONS: Mathematical modelling using a spatially distributed approach for the description of clinical data suggests that alterations both in the capillary wall and in the tissue barrier contribute to UFF through their effect on transport and distribution of solutes and fluid within the tissue.
Asunto(s)
Capilares/metabolismo , Soluciones para Diálisis/farmacocinética , Trasplante de Riñón/efectos adversos , Diálisis Peritoneal Ambulatoria Continua/métodos , Peritoneo/metabolismo , Peritonitis/terapia , Ultrafiltración/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transporte Biológico , Creatinina/metabolismo , Femenino , Francia/epidemiología , Glucosa/metabolismo , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Peritonitis/epidemiología , Peritonitis/etiología , Sistema de Registros , Tasa de Supervivencia/tendencias , Insuficiencia del Tratamiento , Urea/metabolismo , Agua/metabolismo , Adulto JovenRESUMEN
Kidney dialysis patients with sarcopenia have increased mortality. Clinical guidelines recommend peritoneal dialysis (PD) patients have a target daily protein intake to prevent sarcopenia. Protein intake is estimated from total daily urea losses in urine and peritoneal dialysate to assess the protein equivalent of nitrogen appearance rate adjusted for body weight (nPNA). Dietary habits differ among ethnic groups, so we reviewed nPNA and body composition in a multi-ethnic PD population. Body composition was measured with multifrequency bioimpedance in 598 patients (301 white, 136 black, 123 South-Asian, and 38 Asian-Pacific). South-Asians had a lower nPNA compared with white and black individuals (Randerson 0.80 ± 0.21 vs 0.88 ± 0.24 and 0.85 ± 0.24 g/kg/day, Blumenkrantz 0.97 ± 0.14 vs 1.04 ± 0.22 and 0.99 ± 0.22 g/kg/day, Bergström 0.87 ± 0.4 vs 0.95 ± 0.24 and 0.92 ± 0.24 g/kg/day all p < 0.001). South-Asians had lower weights (68.9 ± 14.9 vs 74.4 ± 16.6 and 73.5 ± 16.3 kg, p < 0.001), and although of similar body mass index (25.9 ± 4.9 vs 28.5 ± 4.9 and 26.5 ± 5.2 kg/m2), had both lower skeletal muscle and appendicular muscle mass indexed for height (9.08 ± 1.45 vs 9.89 ± 1.62 and 10.1 ± 1.85, p < 0.001; and 6.95 ± 1.39 vs 7.68 ± 1.48 and 7.67 ± 1.58 kg/m2p < 0.01). South-Asian patients had a lower calculated basal metabolic rate (BMR) (1,358 ± 218 vs 1,487 ± 257 and 1,489 ± 271 kcal/day, p < 0.001).Asian PD patients, particularly South-Asians, have lower dietary protein intakes when calculated by nPNA. However, South-Asians had lower measured muscle mass and calculated BMR. As such, dietary protein intake targets derived from studies in 1 ethnic group are not necessarily applicable for all patients, as those with less muscle mass and lower BMR may well need less daily protein intake to maintain homeostasis.
Asunto(s)
Composición Corporal , Soluciones para Diálisis/farmacocinética , Proteínas en la Dieta/metabolismo , Etnicidad , Fallo Renal Crónico/metabolismo , Diálisis Peritoneal , Femenino , Humanos , Incidencia , Fallo Renal Crónico/etnología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , República de Corea/epidemiologíaRESUMEN
BACKGROUND: Glucose is the most commonly used osmotic medium in peritoneal dialysis (PD) solutions, and its use has been associated with both local and systemic adverse effects. Previous, single-center, observational cohort studies have reported conflicting findings regarding whether a relationship exists between peritoneal glucose exposure and peritoneal small solute transport rate. METHODS: In this secondary analysis of the balANZ multicenter, multinational, randomized controlled trial of a neutral pH, ultra-low glucose degradation product (biocompatible) versus conventional PD solutions over a 2-year period, the relationship between time varying peritoneal glucose exposure and change in peritoneal solute transport rate, (measured as dialysate to plasma creatinine ratio at 4 hours [D:PCr4h]), was evaluated using multivariable, multilevel linear regression. Baseline peritoneal glucose exposure was also assessed as either a continuous or categorical variable. RESULTS: The study included 165 patients (age 58.1 ± 14.2 years, 55% male, 33% diabetic). Peritoneal glucose exposure increased over time (coefficient 1.49, 95% confidence interval [CI] 1.07 - 1.92 and was not significantly associated with change in D:PCr4h (coefficient 0.00004, 95% CI -0.0001 - 0.0002, p = 0.68). Similar results were found when peritoneal glucose exposure was examined as a baseline continuous or categorical variable. A significant 2-way interaction was observed with PD solution type, whereby a progressive increase in D:PCr4h was seen in the patients receiving conventional PD solution, but not in those receiving biocompatible solution. CONCLUSIONS: Increases in peritoneal solute transport rate in PD patients over time were not associated with peritoneal glucose exposure, although a strong and positive association with PD solution glucose degradation product content was identified. Peritoneal glucose exposure may be a less important consideration than peritoneal glucose degradation product exposure with respect to peritoneal membrane function over time.
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Soluciones para Diálisis/farmacocinética , Glucosa/farmacocinética , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Peritoneo/metabolismo , Transporte Biológico , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients. METHODS: The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 µM (110 µg/L) iron via dialysate during hemodialysis session no. 2. RESULTS: Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06-0.10 mg/kg). FPC was well tolerated in the small number of patients studied. CONCLUSIONS: FPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated.
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Anemia Ferropénica/tratamiento farmacológico , Soluciones para Diálisis/farmacocinética , Difosfatos/administración & dosificación , Hematínicos/administración & dosificación , Hierro/administración & dosificación , Insuficiencia Renal Crónica/complicaciones , Administración Intravenosa , Adolescente , Anemia Ferropénica/sangre , Anemia Ferropénica/etiología , Niño , Preescolar , Soluciones para Diálisis/efectos adversos , Soluciones para Diálisis/química , Difosfatos/efectos adversos , Difosfatos/farmacocinética , Estudios de Factibilidad , Femenino , Hematínicos/efectos adversos , Hematínicos/farmacocinética , Hemoglobinas/análisis , Humanos , Lactante , Hierro/efectos adversos , Hierro/sangre , Hierro/farmacocinética , Masculino , Diálisis Renal/métodos , Insuficiencia Renal Crónica/terapia , Resultado del TratamientoRESUMEN
Transforming growth factor-ß1 (TGF-ß1) is a major mediator of peritoneal fibrosis and reportedly affects expression of the H3K4 methyltransferase, SET7/9. SET7/9-induced H3K4 mono-methylation (H3K4me1) critically activates transcription of fibrosis-related genes. In this study, we examined the effect of SET7/9 inhibition on peritoneal fibrosis in mice and in human peritoneal mesothelial cells (HPMCs). We also examined SET7/9 expression in nonadherent cells isolated from the effluent of peritoneal dialysis (PD) patients. Murine peritoneal fibrosis was induced by intraperitoneal injection of methylglyoxal (MGO) into male C57/BL6 mice over 21 days. Sinefungin, a SET7/9 inhibitor, was administered subcutaneously just before MGO injection (10 mg/kg). SET7/9 expression was elevated in both MGO-injected mice and nonadherent cells isolated from the effluent of PD patients. SET7/9 expression was positively correlated with dialysate/plasma ratio of creatinine in PD patients. Sinefungin was shown immunohistochemically to suppress expression of mesenchymal cells and collagen deposition, accompanied by decreased H3K4me1 levels. Peritoneal equilibration tests showed that sinefungin attenuated the urea nitrogen transport rate from plasma and the glucose absorption rate from the dialysate. In vitro, sinefungin suppressed TGF-ß1-induced expression of fibrotic markers and inhibited H3K4me1. These findings suggest that inhibiting the H3K4 methyltransferase SET7/9 ameliorates peritoneal fibrosis.
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Adenosina/análogos & derivados , N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores , Fibrosis Peritoneal/prevención & control , Adenosina/farmacología , Adenosina/uso terapéutico , Animales , Células Cultivadas , Colágeno Tipo I/biosíntesis , Colágeno Tipo I/genética , Soluciones para Diálisis/farmacocinética , Epitelio , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/farmacocinética , Código de Histonas/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/fisiología , Humanos , Masculino , Metilación/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Nitrógeno/farmacocinética , Epiplón/citología , Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/inducido químicamente , Fibrosis Peritoneal/etiología , Regiones Promotoras Genéticas/genética , Piruvaldehído/toxicidad , Factor de Crecimiento Transformador beta1/fisiologíaRESUMEN
Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated.Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin.ResultsIn silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone.Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.
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Soluciones Cristaloides/farmacocinética , Soluciones para Diálisis/farmacocinética , Icodextrina/farmacocinética , Peritoneo/metabolismo , Agua/metabolismo , Animales , Acuaporina 1/genética , Transporte Biológico , Coloides , Simulación por Computador , Soluciones para Diálisis/metabolismo , Genotipo , Glucosa/metabolismo , Icodextrina/metabolismo , Ratones , Modelos Teóricos , Ósmosis , Diálisis PeritonealRESUMEN
BACKGROUND: In end-stage renal disease patients treated with peritoneal dialysis (PD), the osmotic conductance to glucose (OCG) represents the intrinsic ability of the membrane to transport water in response to a crystalloid osmotic gradient. A progressive loss of OCG in long-term PD patients indicates the development of fibrosis in the peritoneal interstitium, and helps identify patients at risk for encapsulating peritoneal sclerosis. The double mini-peritoneal equilibration test (PET) has been proposed as a simple method to assess OCG using the difference in initial ultrafiltration rates generated by 2 successive dwells using 1.36% and 3.86% glucose-based, 1-h PET. However, the presence of a large peritoneal residual volume (RV) may potentially interfere with the correct evaluation of drained volumes, limiting the reliability of OCG assessed by the double mini-PET. METHODS: We retrospectively reviewed data from 53 peritoneal function tests in 35 consecutive PD patients starting PD at our center between March 2013 and March 2017. The test consisted of a uni-PET (double mini-PET combined with a 3.86%, 4-h PET) performed at PD start, then yearly. In addition to peritoneal solute transport rate and net ultrafiltration, the tests provided information about osmotic water transport (OCG, sodium sieving, and free-water transport) as well as the RV estimated from albumin dilution. RESULTS: Contrary to sodium sieving, net ultrafiltration, and free-water transport, OCG did not correlate with any of the other parameters of osmotic water transport. In multivariate regression analyses, the RV was identified as the only determinant of OCG, while it did not alter the robust association between sodium sieving/free-water transport and their respective determinants. Considering only baseline tests or the whole series of tests, the presence of a large intraperitoneal RV was associated with discrepant values between OCG and sodium sieving, and with an artificial increase in OCG. CONCLUSIONS: A large RV leads to significant overestimation of OCG using the double mini-PET, potentially reducing the ability of OCG to identify patients with progressive fibrosis in the peritoneal interstitium. On the other hand, sieving of the dialysate sodium, a biochemical surrogate for OCG, is independent of the RV and may therefore be more reliable. A call for caution is warranted in patients with a large RV to avoid misinterpretation of OCG values derived from the double mini-PET.
Asunto(s)
Glucosa/farmacocinética , Fallo Renal Crónico/terapia , Diálisis Peritoneal/métodos , Peritoneo/metabolismo , Transporte Biológico , Soluciones para Diálisis/farmacocinética , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/metabolismo , Masculino , Persona de Mediana Edad , Ósmosis , Reproducibilidad de los Resultados , Estudios RetrospectivosRESUMEN
BACKGROUND: Incremental dialysis utilizes gradually increasing dialysis doses in response to declines in residual kidney function, and it is the preferred renal replacement therapy for patients who have just transitioned to end-stage renal disease (ESRD). Incremental peritoneal dialysis (PD) may impose fewer restrictions on patients' lifestyle, help attenuate lifetime peritoneal and systemic exposure to glucose and its degradation products, and minimize connections that could compromise the sterile fluid path. In this study, we utilized a 3-pore kinetic model to assess fluid and solute removal during single daily icodextrin treatments for patients with varying glomerular filtration rates (GFR). METHODS: Single icodextrin exchanges of 8 to 16 hours using 2- and 2.5-L bag volumes were simulated for different patient transport types (i.e., high to low) to predict daily peritoneal ultrafiltration (UF), daily peritoneal sodium removal, and weekly total (peritoneal + residual kidney) Kt/V (Kt/VTotal) for patients with residual renal GFRs ranging from 0 to 15 mL/min/1.73 m2. RESULTS: Daily peritoneal UF varied from 359 to 607 mL, and daily peritoneal Na removal varied from 52 to 87 mEq depending on length of icodextrin exchange and bag volume. Both were effectively independent of patient transport type. All but very large patients (total body water [TBW] > 60 L) were predicted to achieve adequate dialysis (Kt/VTotal ≥ 1.7) with a GFR of 10 mL/min/1.73 m2, and small patients (TBW: 30 L) were predicted to achieve adequate dialysis with a GFR of 6 mL/min/1.73 m2. CONCLUSIONS: A single daily icodextrin exchange can be tailored to augment urea, UF, and Na removal in patients with sufficient residual kidney function (RKF). A solitary icodextrin exchange may therefore be reasonable initial therapy for some incident ESRD patients.
Asunto(s)
Soluciones para Diálisis/farmacocinética , Tasa de Filtración Glomerular/fisiología , Icodextrina/farmacocinética , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/terapia , Diálisis Peritoneal , Humanos , Fallo Renal Crónico/fisiopatología , Modelos BiológicosRESUMEN
Steady-state pharmacokinetics of oral ciprofloxacin in 3 continuous cycling peritoneal dialysis (CCPD) outpatients given ciprofloxacin 750 mg b.i.d. for 5 doses was determined. Mean steady-state maximum serum concentration and half-life were 4.4 ± 1.5 mg/L and 10.3 ± 2.6 hours, respectively. Mean maximum dialysate concentration in the daytime long dwell and overnight continuous cycling dwell were 7.4 ± 1.2 mg/L and 3.3 ± 1.2 mg/L, respectively. Oral ciprofloxacin 750 mg b.i.d. may be reasonable for bloodstream and peritoneal infections caused by susceptible bacteria in CCPD patients.
Asunto(s)
Antibacterianos/farmacocinética , Ciprofloxacina/farmacocinética , Soluciones para Diálisis/farmacocinética , Diálisis Peritoneal/efectos adversos , Peritonitis/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Ciprofloxacina/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Peritonitis/etiologíaRESUMEN
The measure of intraperitoneal pressure in peritoneal dialysis is easy and provides clear therapeutic benefits. However it is measured only rarely in adult peritoneal dialysis units. This review aims to disseminate the usefulness of measuring intraperitoneal pressure. This measurement is performed in supine before initiating the drain of a manual exchange with "Y" system, by raising the drain bag and measuring from the mid-axillary line the height of the liquid column that rises from the patient. With typical values of 10-16 cmH2O, intraperitoneal pressure should never exceed 18 cmH2O. With basal values that depend on body mass index, it increases 1-3 cmH2O/L of intraperitoneal volume, and varies with posture and physical activity. Its increase causes discomfort, sleep and breathing disturbances, and has been linked to the occurrence of leaks, hernias, hydrothorax, gastro-esophageal reflux and enteric peritonitis. Less known and valued is its ability to decrease the effectiveness of dialysis significantly counteracting ultrafiltration and decreasing solute clearance to a smaller degree. Because of its easy measurement and potential utility, should be monitored in case of ultrafiltration failure to rule out its eventual contribution in some patients. Although not yet mentioned in the clinical practice guidelines for PD, its clear benefits justify its inclusion among the periodic measurements to consider for prescribing and monitoring peritoneal dialysis.
Asunto(s)
Líquido Ascítico/fisiología , Diálisis Peritoneal/métodos , Presión , Adulto , Índice de Masa Corporal , Soluciones para Diálisis/administración & dosificación , Soluciones para Diálisis/efectos adversos , Soluciones para Diálisis/farmacocinética , Humanos , Presión Hidrostática , Fallo Renal Crónico/terapia , Manometría/métodos , Diálisis Peritoneal/efectos adversos , Valores de Referencia , Posición Supina , UltrafiltraciónRESUMEN
BACKGROUND: The original peritoneal equilibration test (PET) was used to classify peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since been suggested that a 3.86% glucose solution be used because this provides better information about ultrafiltration (UF) capacity and the sodium (Na) sieving of the peritoneal membrane. OBJECTIVE: The aim of this study was to determine reference values for a PET using a 3.86% glucose solution (PET-3.86%). METHODS: We evaluated the PET-3.86% in a large population of incident PD patients attending 27 Italian dialysis centers. RESULTS: We evaluated the results of 758 PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of PD was 5 ± 3 months. The ratio of the concentrations of creatinine in dialysate/plasma (D/PCreat) was 0.73 ± 0.1 (median 0.74). The ratio between the concentrations of glucose at the end/beginning of the test (D/D0) was 0.25 ± 0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill was respectively 776 ± 295 mL (median 781 mL) and 675 ± 308 mL (median 689 mL). Sodium sieving was 8.4 ± 3.8 mmol/L (median 8.0 mmol/L). CONCLUSION: The results of the study provide PET-3.86% reference values for the beginning of PD that can be used to classify PD patients into transport classes and monitor them over time.