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1.
Hemodial Int ; 24(2): 162-174, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31826326

RESUMO

BACKGROUND: Frequent hemodialysis modifies serum phosphorus, blood pressure, and left ventricular mass (LVM). We ascertained whether frequent hemodialysis is associated with specific changes in biomarker profile among patients enrolled in the frequent hemodialysis network (FHN) trials. METHODS: This was a post hoc analysis of biomarkers among patients enrolled to the FHN trials. In particular, we hypothesized that frequent hemodialysis is associated with changes in a specific set of biomarkers which are linked with changes in blood pressure or LVM. RESULTS: Among 332 randomized patients, 243 had biomarker data available. Of these, 124 patients were assigned to 3-times-a-week hemodialysis (94 [Daily Trial] and 30 [Nocturnal Trial]) and 119 patients were assigned to 6-times-a-week hemodialysis (87 [Daily Trial] and 32 [Nocturnal Trial]). Frequent hemodialysis lowered phosphate, blood pressures, LVM, log fibroblast growth factor (FGF)23, and tissue inhibitors of metalloproteinase (TIMP)-2 levels. The fall in phosphate was associated with changes in FGF23 (r = 0.48, P < 0.001) [Daily Trial] and (r = 0.55, P < 0.001) [Nocturnal Trial]) and tended to be associated with changes in systolic blood pressure (r = 0.18, P = 0.057) [Daily Trial] and (r = 0.31, P = 0.04) [Nocturnal Trial]. Within the Daily Trial, changes in MMP2 (r = 0.20, P = 0.034) were associated with changes in LVM. In the Nocturnal Trial, changes in TIMP-1 (r = 0.37, P = 0.029) and MMP 9 (r = -0.38, P = 0.01) were associated with LVM changes. MMP2 changes were associated with changes in systolic blood pressure. CONCLUSIONS: Reduction of serum phosphate by frequent hemodialysis may modulate FGF23 levels and systolic blood pressure. Markers of matrix turnover are associated with LVM changes. Frequent hemodialysis may affect pathological mediators of chronic kidney disease-mineral bone-metabolism disorder.

2.
J Am Soc Nephrol ; 30(9): 1735-1745, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31292197

RESUMO

BACKGROUND: Surrogate end points are needed to assess whether treatments are effective in the early stages of CKD. GFR decline leads to kidney failure, but regulators have not approved using differences in the change in GFR from the beginning to the end of a randomized, controlled trial as an end point in CKD because it is not clear whether small changes in the GFR slope will translate to clinical benefits. METHODS: To assess the use of GFR slope as a surrogate end point for CKD progression, we performed a meta-analysis of 47 RCTs that tested 12 interventions in 60,620 subjects. We estimated treatment effects on GFR slope (mean difference in GFR slope between the randomized groups), for the total slope starting at baseline, chronic slope starting at 3 months after randomization, and on the clinical end point (doubling of serum creatinine, GFR<15 ml/min per 1.73 m2, or ESKD) for each study. We used Bayesian mixed-effects analyses to describe the association of treatment effects on GFR slope with the clinical end point and to test how well the GFR slope predicts a treatment's effect on the clinical end point. RESULTS: Across all studies, the treatment effect on 3-year total GFR slope (median R 2=0.97; 95% Bayesian credible interval [BCI], 0.78 to 1.00) and on the chronic slope (R 2 0.96; 95% BCI, 0.63 to 1.00) accurately predicted treatment effects on the clinical end point. With a sufficient sample size, a treatment effect of 0.75 ml/min per 1.73 m2/yr or greater on total slope over 3 years or chronic slope predicts a clinical benefit on CKD progress with at least 96% probability. CONCLUSIONS: With large enough sample sizes, GFR slope may be a viable surrogate for clinical end points in CKD RCTs.

3.
Eur J Vasc Endovasc Surg ; 57(5): 719-728, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31000459

RESUMO

BACKGROUND: The arteriovenous fistula (AVF) is central to haemodialysis treatment, but up to half of surgically created AVF fail to mature. Chronic kidney disease often leads to mineral metabolism disturbances that may interfere with AVF maturation through adverse vascular effects. This study tested associations between mineral metabolism markers and vein histology at AVF creation and unassisted and overall clinical AVF maturation. METHODS: Concentrations of fibroblast growth factor 23, parathyroid hormone, calcium, phosphate, and vitamin D metabolites: 1,25(OH)2D, 24,25(OH)2D, 25(OH)D, and bioavailable 25(OH)D were measured in pre-operative serum samples from 562 of 602 participants in the Haemodialysis Fistula Maturation Study, a multicentre, prospective cohort study of patients undergoing surgical creation of an autologous upper extremity AVF. Unassisted and overall AVF maturation were ascertained for 540 and 527 participants, respectively, within nine months of surgery or four weeks of dialysis initiation. Study personnel obtained vein segments adjacent to the portion of the vein used for anastomosis, which were processed, embedded, and stained for measurement of neointimal hyperplasia, calcification, and collagen deposition in the medial wall. RESULTS: Participants in this substudy were 71% male, 43% black, and had a mean age of 55 years. Failure to achieve AVF maturation without assistance occurred in 288 (53%) participants for whom this outcome was determined. In demographic and further adjusted models, mineral metabolism markers were not significantly associated with vein histology characteristics, unassisted AVF maturation failure, or overall maturation failure, other than a biologically unexplained association of higher 24,25(OH)2D with overall failure. This exception aside, associations were non-significant for continuous and categorical analyses and relevant subgroups. CONCLUSIONS: Serum concentrations of measured mineral metabolites were not substantially associated with major histological characteristics of veins in patients undergoing AVF creation surgery, or with AVF maturation failure, suggesting that efforts to improve AVF maturation rates should increase attention to other processes such as vein mechanics, anatomy, and cellular metabolism among end stage renal disease patients.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Minerais/sangue , Diálise Renal/métodos , Remodelação Vascular , Adulto , Idoso , Biomarcadores/sangue , Calcificação Fisiológica , Cálcio/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Veias/metabolismo , Veias/patologia , Vitamina D/sangue
4.
Hemodial Int ; 23(3): 297-305, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30861262

RESUMO

INTRODUCTION: Small molecular weight toxin clearance is the main method of assessment of hemodialysis efficiency. Middle molecules including cystatin C (CysC) and Beta-2 microglobulin (ß2-M) are understudied. We hypothesized that lowering of predialysis CysC and ß2-M serum concentrations would be affected by switching to more frequent hemodialysis. METHODS: Predialysis CysC and ß2-M serum concentrations were measured from serum samples of the Frequent Hemodialysis Network (FHN) Daily and Nocturnal Trials. The differences between predialysis concentrations at baseline (while on conventional thrice weekly dialysis) and those after 12-months of study (on more frequent dialysis) were compared separately by trial (Nocturnal, Daily). We tested the associations between predialysis serum CysC and ß2-M concentrations and outcomes. FINDINGS: Forty-nine percent and 52% of the patients from the FHN Daily and Nocturnal Trials respectively were included in this ancillary study. Predialysis serum CysC concentrations remained unchanged after intensifying hemodialysis dose by either modality. There was significant lowering of the serum ß2-M concentrations in the frequent Daily Trial hemodialysis group at 12 months in all patients and in patients without residual renal function at baseline (-3.8 ± 12.62 µg/mL, P = 0.004; -5.9 ± 12.99 µg/mL, P = 0.02, respectively). There were no significant differences between the baseline and the 12-months predialysis ß2-M serum concentrations in the two control groups (Daily 3× and Nocturnal 3× groups). No association between the changes in the two biomarkers between baseline and 12-months and in changes in left ventricular mass, physical-health composite scores, hospitalization rate, and death were found. The numbers of hospitalizations and deaths were small. DISCUSSION: ß2-M may be a better biomarker of dialysis dose than CysC. Reduction in the concentration of potentially toxic long-lived proteins of the size of ß-2M is one potential long-term benefit of more intensive dialysis that may be explored.

5.
Chest ; 155(2): 288-296, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29940164

RESUMO

BACKGROUND: The natural history of lymphangioleiomyomatosis (LAM) is mainly derived from retrospective cohort analyses, and it remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. METHODS: A linear mixed effects model was used to compute the rate of decline of FEV1 and to identify variables affecting FEV1 decline among 217 registry patients who enrolled from 1998 to 2001. Prognostic variables associated with progression to death/lung transplantation were identified by using a Cox proportional hazards model. RESULTS: Mean annual decline of FEV1 was 89 ± 53 mL/year and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scanning (P = .02) and in premenopausal subjects (118 mL/year) compared with postmenopausal subjects (74 mL/year) (P = .003). There were 26 deaths and 43 lung transplantations during the evaluation period. The estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 94%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio, 0.30; P = .0002) and higher baseline FEV1 (hazard ratio, 0.97; P = .008) or diffusion capacity of lung for carbon monoxide (hazard ratio, 0.97; P = .001) were independently associated with a lower risk of progression to death or lung transplantation. CONCLUSIONS: The median transplant-free survival in patients with LAM is > 20 years. Menopausal status, as well as structural and physiologic markers of disease severity, significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM.


Assuntos
Progressão da Doença , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Linfangioleiomiomatose/patologia , Linfangioleiomiomatose/cirurgia , Sistema de Registros , Fatores Etários , Biomarcadores/análise , Feminino , Volume Expiratório Forçado , Humanos , Lipopolissacarídeos/metabolismo , Estudos Longitudinais , Neoplasias Pulmonares/mortalidade , Linfangioleiomiomatose/mortalidade , Menopausa/fisiologia , National Heart, Lung, and Blood Institute (U.S.) , Prognóstico , Estudos Prospectivos , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Estados Unidos
6.
Int J Cancer ; 144(3): 448-458, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30117164

RESUMO

Calcium supplementation (1,200 mg/day) did not significantly reduce colorectal adenomas in our recent randomized, controlled trial (Vitamin D/Calcium Polyp Prevention Study, VCPPS, 2004-2013) in contrast to our previous trial (Calcium Polyp Prevention Study, CPPS, 1988-1996). To reconcile these findings, we identified participant characteristics that differed between the study populations and modified the effect of calcium supplementation on adenomas or high-risk findings (advanced or multiple adenomas). Compared to the CPPS, more participants in the VCPPS were obese (body mass index (BMI) ≥30 kg/m2 ; 37.5% vs. 24.4%) and fewer had normal BMI (BMI <25 kg/m2 ; 18.5% vs. 31%). BMI appeared to modify the effect of calcium supplementation on adenomas and especially on high risk-findings: in the VCPPS, there was a 44% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.56, 95% CI = 0.26-1.23), but not among overweight (RR = 1.09, 95% CI = 0.62-1.91) or obese (RR = 1.54, 95% CI = 0.92-2.57) individuals (pinteraction = 0.03). Similarly, in the CPPS, there was a 56% reduction in high-risk findings among individuals whose BMI was normal (RR = 0.44, 95% CI = 0.26-0.74), but not among overweight (RR = 0.87, 95% CI = 0.55-1.39) or obese (RR = 1.02, 95% CI = 0.57-1.82) individuals (pinteraction = 0.02). Standardization of each trial's findings to the BMI distribution in the other attenuated calcium's protective effect on adenomas in the CPPS but enhanced it in the VCPPS. In conclusion, 1,200 mg/day calcium supplementation may reduce risk of colorectal adenomas among those with normal BMI but not in overweight or obese individuals; and differences in BMI distribution partially account for the apparent difference in calcium efficacy between the two trials.


Assuntos
Adenoma/epidemiologia , Índice de Massa Corporal , Carbonato de Cálcio/administração & dosagem , Neoplasias Colorretais/epidemiologia , Adenoma/prevenção & controle , Neoplasias Colorretais/prevenção & controle , Suplementos Nutricionais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Estados Unidos/epidemiologia
7.
Nephrology (Carlton) ; 24(1): 81-87, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29064128

RESUMO

AIM: Correction of metabolic acidosis in patients with chronic kidney disease has been associated with improvement in thyroid function. We examined whether changes in bicarbonate were associated with changes in thyroid function in patients with end-stage renal disease receiving conventional or more frequent haemodialysis. METHODS: In the Frequent Hemodialysis Network Trials, the relationship between changes in serum bicarbonate, free triiodothyronine (FT3) and free thyroxine (FT4) was examined among 147 and 48 patients with endogenous thyroid function who received conventional (3×/week) or more frequent (6×/week) haemodialysis (Daily Trial) or who received conventional or more frequent nocturnal haemodialysis (Nocturnal Trial). Equilibrated normalized protein catabolic rate (enPCR) was examined to account for nutritional factors affecting both acid load and thyroid function. RESULTS: Increasing dialysis frequency was associated with increased bicarbonate level. Baseline bicarbonate level was not associated with baseline FT3 and FT4. Change in bicarbonate level was not associated with changes in FT3 and FT4 in the Daily Trial nor for FT4 in the Nocturnal Trial (r ≤ 0.14, P > 0.21). While, a significant correlation between change in serum bicarbonate and change in FT3 (r = 0.44, P = 0.02) was observed in the Nocturnal Trial; findings were no longer significant after adjusting for change in enPCR (r = 0.37, P = 0.08). For participants with baseline bicarbonate <23 mmol/L, no association between change in bicarbonate and change in thyroid indices were seen in the Daily Trial; for the Nocturnal Trial, findings were also not significant for change in FT3 and the association between change in bicarbonate and change in FT4 (r = 0.54, P = 0.03) was no longer significant after adjusting for enPCR (r = 0.45, P = 0.11). CONCLUSION: Changes in bicarbonate were not associated with changes in thyroid hormone levels after adjusting for enPCR, as a marker of nutritional status. Future studies should examine whether improvement in acid base status improves thyroid function in haemodialysis patients with evidence of thyroid hypofunction.


Assuntos
Equilíbrio Ácido-Base , Bicarbonatos/sangue , Hemodiálise no Domicílio/métodos , Falência Renal Crônica/terapia , Diálise Renal/métodos , Glândula Tireoide/metabolismo , Tiroxina/sangue , Tri-Iodotironina/sangue , Acidose/sangue , Acidose/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Feminino , Hemodiálise no Domicílio/efeitos adversos , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Estudos Prospectivos , Desnutrição Proteico-Calórica/sangue , Desnutrição Proteico-Calórica/fisiopatologia , Diálise Renal/efeitos adversos , Glândula Tireoide/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
8.
J Am Soc Nephrol ; 29(11): 2735-2744, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309898

RESUMO

BACKGROUND: The utility of early postoperative ultrasound measurements in predicting arteriovenous fistula (AVF) clinical maturation is uncertain. METHODS: We investigated the relationships of ultrasound parameters with AVF clinical maturation in newly created AVF, measured at 1 day and 2 and 6 weeks, in 602 participants of a multicenter, observational cohort study. A backward elimination algorithm identified ultrasound measurements that independently predicted unassisted and overall AVF maturation. Candidate variables included AVF blood flow, diameter, and depth, upper arm arterial diameter, presence of stenosis, presence of accessory veins, seven case-mix factors (age, sex, black race, AVF location, diabetes, dialysis status, and body mass index), and clinical center. We evaluated the accuracy of the resulting models for clinical prediction. RESULTS: At each ultrasound measurement time, AVF blood flow, diameter, and depth each predicted in a statistically significant manner both unassisted and overall clinical maturation. Moreover, neither the remaining ultrasound parameters nor case-mix factors were associated with clinical AVF maturation after accounting for blood flow, diameter, and depth, although maturation probabilities differed among clinical centers before and after accounting for these parameters. The crossvalidated area under the receiver operating characteristic curve for models constructed using these three ultrasound parameters was 0.69, 0.74, and 0.79 at 1 day and 2 and 6 weeks, respectively, for unassisted AVF clinical maturation and 0.69, 0.71, and 0.76, respectively, for overall AVF maturation. CONCLUSIONS: AVF blood flow, diameter, and depth moderately predicted unassisted and overall AVF clinical maturation. The other factors considered did not further improve AVF maturation prediction.


Assuntos
Derivação Arteriovenosa Cirúrgica , Diálise Renal/métodos , Grau de Desobstrução Vascular , Adulto , Idoso , Algoritmos , Velocidade do Fluxo Sanguíneo , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiologia , Artéria Braquial/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Ultrassonografia
9.
Am J Nephrol ; 48(1): 56-64, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30071516

RESUMO

BACKGROUND: The arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. However, approximately half of AVFs fail to mature. The use of angiotensin converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs) exerts favorable endothelial effects and may promote AVF maturation. We tested associations of ACE-I and ARBs, CCBs, beta-blockers, and diuretics with the maturation of newly created AVFs. METHODS: We evaluated 602 participants from the Hemodialysis Fistula Maturation Study, a multi-center, prospective cohort study of AVF maturation. We ascertained the use of each medication class within 45 days of AVF creation surgery. We defined maturation outcomes by clinical use within 9 months of surgery or 4 weeks of initiating hemodialysis. RESULTS: Unassisted AVF maturation failure without intervention occurred in 54.0% of participants, and overall AVF maturation failure (with or without intervention) occurred in 30.1%. After covariate adjustment, CCB use was associated with a 25% lower risk of overall AVF maturation failure (95% CI 3%-41% lower) but a non-significant 10% lower risk of unassisted maturation failure (95% CI 23% lower to 5% higher). ACE-I/ARB, beta-blocker, and diuretic use was not significantly associated with AVF maturation outcomes. None of the antihypertensive medication classes were associated with changes in AVF diameter or blood flow over 6 weeks following surgery. CONCLUSIONS: CCB use may be associated with a lower risk of overall AVF maturation failure. Further studies are needed to determine whether CCBs might play a causal role in improving AVF maturation outcomes.


Assuntos
Anti-Hipertensivos/administração & dosagem , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Falência Renal Crônica/terapia , Grau de Desobstrução Vascular/efeitos dos fármacos , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Diálise Renal/métodos , Falha de Tratamento
10.
Clin J Am Soc Nephrol ; 13(8): 1225-1233, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30045914

RESUMO

BACKGROUND AND OBJECTIVES: HDL particles obtained from patients on chronic hemodialysis exhibit lower cholesterol efflux capacity and are enriched in inflammatory proteins compared with those in healthy individuals. Observed alterations in HDL proteins could be due to effects of CKD, but also may be influenced by the hemodialysis procedure, which stimulates proinflammatory and prothrombotic pathways. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We compared HDL-associated proteins in 143 participants who initiated hemodialysis within the previous year with those of 110 participants with advanced CKD from the Hemodialysis Fistula Maturation Study. We quantified concentrations of 38 HDL-associated proteins relative to total HDL protein using targeted mass spectrometry assays that included a stable isotope-labeled internal standard. We used linear regression to compare the relative abundances of HDL-associated proteins after adjustment and required a false discovery rate q value ≤10% to control for multiple testing. We further assessed the association between hemodialysis initiation and cholesterol efflux capacity in a subset of 80 participants. RESULTS: After adjustment for demographics, comorbidities, and other clinical characteristics, eight HDL-associated proteins met the prespecified false discovery threshold for association. Recent hemodialysis initiation was associated with higher HDL-associated concentrations of serum amyloid A1, A2, and A4; hemoglobin-ß; haptoglobin-related protein; cholesterylester transfer protein; phospholipid transfer protein; and apo E. The trend for participants recently initiating hemodialysis for lower cholesterol efflux capacity compared with individuals with advanced CKD did not reach statistical significance. CONCLUSIONS: Compared with advanced CKD, hemodialysis initiation within the previous year is associated with higher concentrations of eight HDL proteins related to inflammation and lipid metabolism. Identified associations differ from those recently observed for nondialysis-requiring CKD. Hemodialysis initiation may further impair cholesterol efflux capacity. Further work is needed to clarify the clinical significance of the identified proteins with respect to cardiovascular risk. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_07_25_CJASNPodcast_18_8_W.mp3.


Assuntos
Lipoproteínas HDL/química , Diálise Renal , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/metabolismo
11.
Am J Nephrol ; 47(3): 208-217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29621747

RESUMO

BACKGROUND: Regression of left ventricular hypertrophy (LVH) is feasible with more frequent hemodialysis (HD). We aimed to ascertain pathways associated with regression of left ventricular mass (LVM) in patients enrolled in the Frequent HD Network (FHN) trials. METHODS: This was a post hoc observational cohort study. We hypothesized LVH regression with frequent HD was associated with a different cardiovascular biomarker profile. Regressors were defined as patients who achieved a reduction of more than 10% in LVM at 12 months. Progressors were defined as patients who had a minimum of 10% increase in LVM at 12 months. RESULTS: Among 332 randomized patients, 243 had biomarker data available. Of these, 121 patients did not progress or regress, 77 were regressors, and 45 were progressors. Mean LVM change differed between regressors and progressors by -65.6 (-74.0 to -57.2) g, p < 0.001. Regressors had a median (interquartile range) increase in dialysis frequency (from 3.0 [3.0-3.0] to 4.9 [3-5.7] per week, p = 0.001) and reductions in pre-dialysis systolic (from 149.0 [136.0-162.0] to 136.0 [123.0-152.0] mm Hg, p < 0.001) and diastolic (from 83.0 [71.0-91.0] to 76.0 [68.0-84.0] mm Hg, p < 0.001) blood pressures. Klotho levels increased in regressors versus progressors (76.9 [10.5-143.3] pg/mL, p = 0.024). Tissue inhibitors of metalloproteinase (TIMP)-2 levels fell in regressors compared to progressors (-7,853 [-14,653 to -1,052] pg/mL, p = 0.024). TIMP-1 and log (brain natriuretic -peptide [BNP]) levels also tended to fall in regressors. Changes in LVM correlated inversely with changes in klotho (r = -0.24, p = 0.014). -Conclusions: Markers of collagen turnover and changes in klotho levels are potential novel pathways associated with regression of LVH in the dialysis population, which will require further prospective validation.


Assuntos
Biomarcadores/sangue , Hipertrofia Ventricular Esquerda/terapia , Falência Renal Crônica/complicações , Diálise Renal , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertrofia Ventricular Esquerda/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão
12.
Am J Kidney Dis ; 71(5): 677-689, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29398178

RESUMO

BACKGROUND: Half of surgically created arteriovenous fistulas (AVFs) require additional intervention to effectively support hemodialysis. Postoperative care and complications may affect clinical maturation. STUDY DESIGN: Hemodialysis Fistula Maturation (HFM) Study, a 7-center prospective cohort study. SETTING & PARTICIPANTS: 491 patients with single-stage AVFs who had neither thrombosis nor AVF intervention before a 6-week postoperative ultrasonographic examination and who required maintenance hemodialysis. PREDICTORS: Postoperative care processes and complications. OUTCOMES: Attempted cannulation, successful cannulation, and unassisted and overall clinical maturation as defined by the HFM Study criteria. RESULTS: AVF cannulation was attempted in 443 of 491 (90.2%) participants and was eventually successful in 430 of these 443 (97.1%) participants. 263 of these 430 (61.2%) reached unassisted and 118 (27.4%) reached assisted AVF maturation (overall maturation, 381/430 [88.6%]). Attempted cannulation was less likely in patients of surgeons with policies for routine 2-week versus later-than-2-week first postoperative visits (OR, 0.21; 95% CI, 0.06-0.70), routine second postoperative follow-up visits (OR, 0.39; 95% CI, 0.15-0.97), and a routine clinical postoperative ultrasound (OR, 0.28; 95% CI, 0.14-0.55). Attempted cannulation was also less likely among patients undergoing procedures to assist maturation (OR, 0.51; 95% CI, 0.27-0.98). Unassisted maturation was more likely for patients treated in facilities with access coordinators (OR, 1.91; 95% CI, 1.17-3.12), but less likely after precannulation nonstudy ultrasounds (OR per ultrasound, 0.42 [95% CI, 0.26-0.68]) and initial unsuccessful cannulation attempts (OR per each additional attempt, 0.90 [95% CI, 0.83-0.98]). Overall maturation was less likely with infiltration before successful cannulation (OR, 0.44; 95% CI, 0.22-0.89). Among participants receiving maintenance hemodialysis before AVF surgery, unassisted and overall maturation were less likely with longer intervals from surgery to initial cannulation (ORs for each additional month of 0.81 [95% CI, 0.76-0.88] and 0.93 [95% CI, 0.89-0.98], respectively) and from initial to successful cannulation (ORs for each additional week of 0.87 [95% CI, 0.81-0.94] and 0.88 [95% CI, 0.83-0.94], respectively). LIMITATIONS: Surgeons' management policies were assessed only by questionnaire at study onset. Most participants received upper-arm AVFs, planned 2-stage AVFs were excluded, and maturation time windows were imposed. Some care processes may have been missed and the observational design limits causal attribution. CONCLUSIONS: Multiple processes of care and complications are associated with AVF maturation outcomes.


Assuntos
Fístula Arteriovenosa/cirurgia , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Cateterismo/métodos , Falência Renal Crônica/reabilitação , Diálise Renal/efeitos adversos , Dispositivos de Acesso Vascular/efeitos adversos , Adulto , Idoso , Fístula Arteriovenosa/diagnóstico por imagem , Estudos de Coortes , Remoção de Dispositivo/métodos , Feminino , Seguimentos , Humanos , Falência Renal Crônica/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Diálise Renal/métodos , Reoperação/métodos , Medição de Risco , Resultado do Tratamento , Ultrassonografia Doppler/métodos
13.
Clin Exp Nephrol ; 22(2): 299-308, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28741050

RESUMO

BACKGROUND: Two randomized, double-blind, placebo-controlled trials (EPPIC-1 and EPPIC-2) investigated the efficacy and safety of AST-120, an oral spherical carbon adsorbent, in adults with chronic kidney disease (CKD). While the benefit of adding AST-120 to standard therapy was not supported by these trials, we performed a post hoc analysis to focus on CKD progression and to determine the risk factors for the primary endpoint in the EPPIC trial population. METHODS: In the EPPIC trials, patients were randomly assigned 1:1 to treatment with AST-120 or placebo. The primary endpoint was a composite of dialysis initiation, kidney transplantation, or doubling of serum creatinine. The EPPIC trial pooled population was evaluated with the same statistical methods used for analysis of the primary and secondary efficacy endpoints. The trials were registered on ClinicalTrials.gov (NCT00500682 [EPPIC-1] and NCT00501046 [EPPIC-2]). RESULTS: An analysis of the placebo population suggested baseline urinary protein to urinary creatinine ratio (UP/UCr) ≥1.0 and hematuria were independent risk factors for event occurrence and eGFR lowering. Analysis of the high risk patients revealed a difference in the primary endpoint occurrence between treatment groups, if angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers were administered (hazard ratio 0.74, 95% confidence interval 0.56-0.96). Also, the eGFR changes from baseline in the AST-120 group were smaller than that in the placebo group (P = 0.035). CONCLUSIONS: CKD progression may have an association with baseline UP/UCr and hematuria. Treatment with AST-120 may delay the time to the primary endpoint in patients with progressive CKD receiving standard therapy, thus warranting further investigation.


Assuntos
Carbono/uso terapêutico , Rim/efeitos dos fármacos , Óxidos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Carbono/efeitos adversos , Creatinina/sangue , Creatinina/urina , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Hematúria/etiologia , Hematúria/terapia , Humanos , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Óxidos/efeitos adversos , Proteinúria/etiologia , Proteinúria/terapia , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
15.
J Am Soc Nephrol ; 28(10): 3076-3088, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28724774

RESUMO

Stenosis from venous neointimal hyperplasia is common in native arteriovenous fistulas (AVFs). However, the preexisting histologic characteristics of veins at fistula creation, and associations thereof with baseline patient factors, have not been well characterized. In this study, we conducted histologic analysis of a segment of the vein used for anastomosis creation, obtained during AVF creation from 554 of the 602 participants in the multicenter Hemodialysis Fistula Maturation Cohort Study. We quantified intimal and medial areas and lengths of the internal and external elastic lamina by morphometry and assessed venous wall cells by immunohistochemistry, extracellular matrix with Movat stain, and calcium deposition by alizarin red stain. We also studied a representative subset of veins for markers of monocyte/macrophage content, cell proliferation, apoptosis, and neoangiogenesis. Neointima occupied >20% of the lumen in 57% of fully circumferential vein samples, and neointimal hyperplasia associated positively with age and inversely with black race. The neointima was usually irregularly thickened, sometimes concentric, and contained α-smooth muscle actin-expressing cells of smooth muscle or myofibroblast origin. Proteoglycans admixed with lesser amounts of collagen constituted the predominant matrix in the neointima. In 82% of vein samples, the media of vessel walls contained large aggregates of collagen. A minority of veins expressed markers of inflammation, cell proliferation, cell death, calcification, or neoangiogenesis. In conclusion, we observed preexisting abnormalities, including neointimal hyperplasia and prominent accumulation of extracellular matrix, in veins used for AVF creation from a substantial proportion of this cohort.


Assuntos
Derivação Arteriovenosa Cirúrgica , Neointima/patologia , Calcificação Vascular/patologia , Veias/patologia , Adulto , Idoso , Feminino , Humanos , Falência Renal Crônica/patologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal
16.
Am J Respir Crit Care Med ; 195(12): 1661-1670, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28430547

RESUMO

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.


Assuntos
Hipertensão Pulmonar/terapia , Medicina de Precisão/métodos , Educação , Humanos , National Heart, Lung, and Blood Institute (U.S.) , Estados Unidos
17.
Hemodial Int ; 21(4): 534-541, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28301073

RESUMO

INTRODUCTION: End-stage renal disease (ESRD) is associated with perturbations in thyroid hormone concentrations and an increased prevalence of hypothyroidism. Few studies have examined the effects of hemodialysis dose or frequency on endogenous thyroid function. METHODS: Within the Frequent Hemodialysis Network (FHN) trials, we examined the prevalence of hypothyroidism in patients with ESRD. Among those with endogenous thyroid function (without overt hyper/hypothyroidism or thyroid hormone supplementation), we examined the association of thyroid hormone concentration with multiple parameters of self-reported health status, and physical and cognitive performance, and the effects of hemodialysis frequency on serum thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) levels. Conventional thrice-weekly hemodialysis was compared to in-center (6 d/wk) hemodialysis (Daily Trial) and Nocturnal (6 nights/wk) home hemodialysis (Nocturnal Trial) over 12 months. FINDINGS: Among 226 FHN Trial participants, the prevalence of hypothyroidism was 11% based on thyroid hormone treatment and/or serum TSH ≥8 mIU/mL. Among the remaining 195 participants (147 Daily, 48 Nocturnal) with endogenous thyroid function, TSH concentrations were modestly (directly) correlated with age (r = 0.16, P = 0.03) but not dialysis vintage. Circulating thyroid hormone levels were not associated with parameters of health status or physical and cognitive performance. Furthermore, frequent in-center and nocturnal hemodialysis did not significantly change (baseline to month 12) TSH, FT4, or FT3 concentrations in patients with endogenous thyroid function. DISCUSSION: Among patients receiving hemodialysis without overt hyper/hypothyroidism or thyroid hormone treatment, thyroid indices were not associated with multiple measures of health status and were not significantly altered with increased dialysis frequency.


Assuntos
Hipotireoidismo/etiologia , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Testes de Função Tireóidea/métodos , Glândula Tireoide/patologia , Idoso , Feminino , Humanos , Hipotireoidismo/patologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos
18.
Kidney Int ; 91(5): 1186-1192, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28089366

RESUMO

The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.9 hours and 30 trial patients who received six-times weekly in-center hemodialysis for an average of 14.6 hours. Metabolomic analysis revealed that increased treatment frequency and time resulted in an average reduction of only 15 percent in the levels of 107 uremic solutes. Quantitative assays confirmed that increased treatment did not significantly reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate. Kinetic modeling suggested that our ability to lower solute concentrations by increasing hemodialysis frequency and duration may be limited by the presence of non-dialytic solute clearances and/or changes in solute production. Thus, failure to achieve larger reductions in uremic solute concentrations may account, in part, for the limited benefits observed with increasing frequency and weekly treatment time in Frequent Hemodialysis Daily Trial participants.


Assuntos
Cresóis/sangue , Indicã/sangue , Falência Renal Crônica/terapia , Diálise Renal/métodos , Ésteres do Ácido Sulfúrico/sangue , Uremia/sangue , Adulto , Feminino , Humanos , Falência Renal Crônica/sangue , Masculino , Metabolômica , Pessoa de Meia-Idade , Fatores de Tempo
19.
Hemodial Int ; 21(2): 190-196, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27774730

RESUMO

INTRODUCTION: End-stage renal disease is associated with elevations in circulating prolactin concentrations, but the association of prolactin concentrations with intermediate health outcomes and the effects of hemodialysis frequency on changes in serum prolactin have not been examined. METHODS: The FHN Daily and Nocturnal Dialysis Trials compared the effects of conventional thrice weekly hemodialysis with in-center daily hemodialysis (6 days/week) and nocturnal home hemodialysis (6 nights/week) over 12 months and obtained measures of health-related quality of life, self-reported physical function, mental health and cognition. Serum prolactin concentrations were measured at baseline and 12-month follow-up in 70% of the FHN Trial cohort to examine the associations among serum prolactin concentrations and physical, mental and cognitive function and the effects of hemodialysis frequency on serum prolactin. FINDINGS: Among 177 Daily Trial and 60 Nocturnal Trial participants with baseline serum prolactin measurements, the median serum prolactin concentration was 65 ng/mL (25th-75th percentile 48-195 ng/mL) and 81% had serum prolactin concentrations >30 ng/mL. While serum prolactin was associated with sex (higher in women), we observed no association between baseline serum prolactin and age, dialysis vintage, and baseline measures of physical, mental and cognitive function. Furthermore, there was no significant effect of hemodialysis frequency on serum prolactin in either of the two trials. DISCUSSION: Serum prolactin concentrations were elevated in the large majority of patients with ESRD, but were not associated with several measures of health status. Circulating prolactin levels also do not appear to decrease in response to more frequent hemodialysis over a one-year period.


Assuntos
Hiperprolactinemia/etiologia , Falência Renal Crônica/complicações , Diálise Renal/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida
20.
Am J Kidney Dis ; 69(3): 341-349, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27233381

RESUMO

BACKGROUND: Low urine potassium excretion, as a surrogate for dietary potassium intake, is associated with higher risk for hypertension and cardiovascular disease in a general population. Few studies have investigated the relationship of urine potassium with clinical outcomes in chronic kidney disease (CKD). STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: The MDRD (Modification of Diet in Renal Disease) Study was a randomized controlled trial (N = 840) conducted in 1989 to 1993 to examine the effects of blood pressure control and dietary protein restriction on kidney disease progression in adults aged 18 to 70 years with CKD stages 2 to 4. This post hoc analysis included 812 participants. PREDICTOR: The primary predictor variable was 24-hour urine potassium excretion, measured at baseline and at multiple time points (presented as time-updated average urine potassium excretion). OUTCOMES: Kidney failure, defined as initiation of dialysis therapy or transplantation, was determined from US Renal Data System data. All-cause mortality was assessed using the National Death Index. RESULTS: Median follow-up for kidney failure was 6.1 (IQR, 3.5-11.7) years, with 9 events/100 patient-years. Median all-cause mortality follow-up was 19.2 (IQR, 10.8-20.6) years, with 3 deaths/100 patient-years. Baseline mean urine potassium excretion was 2.39±0.89 (SD) g/d. Each 1-SD higher baseline urine potassium level was associated with an adjusted HR of 0.95 (95% CI, 0.87-1.04) for kidney failure and 0.83 (95% CI, 0.74-0.94) for all-cause mortality. Results were consistent using time-updated average urine potassium measurements. LIMITATIONS: Analyses were performed using urine potassium excretion as a surrogate for dietary potassium intake. Results are obtained from a primarily young, nondiabetic, and advanced CKD population and may not be generalizable to the general CKD population. CONCLUSIONS: Higher urine potassium excretion was associated with lower risk for all-cause mortality, but not kidney failure.


Assuntos
Potássio/urina , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/urina , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia
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