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1.
Nephrol Dial Transplant ; 35(5): 846-853, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879076

RESUMO

BACKGROUND: Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known. METHODS: We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF. The hemodialysis study excluded patients with urinary urea clearance >1.5 mL/min, below which RKF was considered to be 'clinically negligible'. We measured eight nonurea solutes from 1280 patients participating in this study and calculated the relative difference in solute levels among patients with and without RKF based on measured urinary urea clearance. RESULTS: The mean age of the participants was 57 years and 57% were female. At baseline, 34% of the included participants had clinically negligible RKF (mean 0.7 ± 0.4 mL/min) and 66% had no RKF. Seven of the eight nonurea solute levels measured were significantly lower in patients with RKF than in those without RKF, ranging from -24% [95% confidence interval (CI) -31 to -16] for hippurate, -7% (-14 to -1) for trimethylamine-N-oxide and -4% (-6 to -1) for asymmetric dimethylarginine. The effect of RKF on plasma levels was comparable or more pronounced than that achieved with a 31% higher dialysis dose (spKt/Vurea 1.7 versus 1.3). Preserved RKF at 1-year follow-up was associated with a lower risk of cardiac death and first cardiovascular event. CONCLUSIONS: Even at very low levels, RKF is not 'negligible', as it continues to provide nonurea solute clearance. Management of patients with RKF should consider these differences.

2.
Pediatr Nephrol ; 35(2): 305-312, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31728748

RESUMO

BACKGROUND: Dialysis in children as well as adults is prescribed to achieve a target spKt/Vurea, where Vurea is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than Vurea which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/Vurea since they have higher BSA relative to body weight. This study measured levels of pseudouridine (PU), a novel marker solute whose production is closely proportional to BSA, to test whether prescription of dialysis to a target spKt/Vurea results in higher plasma levels of PU in smaller children. METHODS: PU and urea nitrogen (ureaN) were measured in plasma and dialysate at the midweek hemodialysis session in 20 pediatric patients, with BSA ranging from 0.65-1.87m2. Mathematical modeling was employed to estimate solute production rates and average plasma solute levels. RESULTS: The dialytic clearance (Kd) of PU was proportional to that of ureaN (average KdPU/KdUreaN 0.69 ± 0.13, r2 0.84, p < 0.001). Production of PU rose in proportion with BSA (r2 0.57, p < 0.001). The pretreatment plasma level of PU was significantly higher in smaller children (r2 0.20, p = 0.051) while the pretreatment level of ureaN did not vary with size. CONCLUSIONS: Prescribing dialysis based on urea kinetics may leave uremic solutes at higher levels in small children. Measurement of a solute produced proportional to BSA may provide a better index of dialysis adequacy than measurement of urea.

3.
4.
Am J Physiol Renal Physiol ; 317(2): F296-F302, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141401

RESUMO

The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; n = 10) or bilateral nephrectomy (n = 10) and analyzed using an established metabolomic platform. Two hundred forty-eight solutes were identified as uremic based on their accumulation in the plasma ultrafiltrate of nephrectomized compared with control rats. CSF levels of 124 of these solutes were sufficient to allow calculation of CSF-to-plasma ultrafiltrate concentration ratios. Levels of many of the uremic solutes were normally lower in the CSF than in the plasma ultrafiltrate, indicating exclusion of these solutes from the brain. CSF levels of the great majority of the uremic solutes increased in renal failure. The increase in the CSF was, however, relatively less than in the plasma ultrafiltrate for most solutes. In particular, for the 31 uremic solutes with CSF-to-plasma ultrafiltrate ratios of <0.25 in control rats, the average CSF-to-plasma ultrafiltrate ratio decreased from 0.13 ± 0.07 in control rats to 0.09 ± 0.06 in nephrectomized rats, revealing sustained ability to exclude these solutes from the brain. In summary, levels of many uremic solutes are normally kept lower in the CSF than in the plasma ultrafiltrate by the action of the blood-brain and blood-CSF barriers. These barriers remain functional but cannot prevent accumulation of uremic solutes in the CSF when the kidneys fail.


Assuntos
Lesão Renal Aguda/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Uremia/líquido cefalorraquidiano , Lesão Renal Aguda/sangue , Lesão Renal Aguda/complicações , Lesão Renal Aguda/fisiopatologia , Animais , Biomarcadores/sangue , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiopatologia , Encefalopatias/sangue , Encefalopatias/etiologia , Encefalopatias/fisiopatologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Progressão da Doença , Rim/metabolismo , Rim/fisiopatologia , Masculino , Metabolômica/métodos , Nefrectomia , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Uremia/sangue , Uremia/etiologia , Uremia/fisiopatologia
6.
Semin Dial ; 32(3): 201-204, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30836447

RESUMO

Intradialytic hypotension (IDH) is a prevalent yet serious complication of hemodialysis, associated with decreased quality of life, inadequate dialysis, vascular access thrombosis, global hypoperfusion, and increased cardiovascular and all-cause mortality. Current guidelines recommend antihypertensive medications be given at night and held the morning of dialysis for affected patients. Despite little evidence to support this recommendation, more than half of patients on dialysis may employ some form of this method. In this article, we will review the available evidence and clinical considerations regarding timing of blood pressure medications and occurrence of IDH, and conclude that witholding BP medications before hemodialysis should not be a routine practice.


Assuntos
Anti-Hipertensivos/administração & dosagem , Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Hipotensão/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Esquema de Medicação , Humanos , Hipotensão/etiologia , Falência Renal Crônica/complicações , Fatores de Tempo , Suspensão de Tratamento
7.
Clin J Am Soc Nephrol ; 13(9): 1398-1404, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30087103

RESUMO

BACKGROUND AND OBJECTIVES: Colon microbial metabolism produces solutes that are normally excreted in the urine and accumulate in the plasma when the kidneys fail. This study sought to further identify and characterize human colon-derived uremic solutes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Colon-derived solutes normally excreted in the urine were identified by comparing urine from controls (n=17) and patients with total colectomies (n=12), using an established metabolomic platform. Colon-derived solutes that accumulate in kidney failure were then identified by comparing the plasma of the control patients with that of patients on dialysis (n=14). RESULTS: Ninety-one urinary solutes were classified as colon-derived on the basis of the finding of a urine excretion rate at least four-fold higher in control patients than in patients with total colectomies. Forty-six were solutes with known chemical structure, 35 of which had not previously been identified as colon-derived. Sixty of the colon-derived solutes accumulated in the plasma of patients with ESKD to a degree greater than urea and were therefore classified as uremic. The estimated urinary clearance for 27 out of the 32 colon-derived solutes for which clearance could be calculated exceeded that of creatinine, consistent with tubular secretion. Sulfatase treatment revealed that 42 out of the 91 colon-derived solutes detected were likely conjugates. CONCLUSIONS: Metabolomic analysis identified numerous colon-derived solutes that are normally excreted in human urine. Clearance by tubular secretion limits plasma levels of many colon-derived solutes.


Assuntos
Colo/metabolismo , Colo/microbiologia , Uremia/urina , Feminino , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade
8.
Toxins (Basel) ; 10(6)2018 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-29865226

RESUMO

Uremic solutes contribute to cardiovascular disease in renal insufficiency. In this review we describe the clearance of selected uremic solutes, which have been associated with cardiovascular disease. These solutes-indoxyl sulfate (IS), p-cresol sulfate (PCS), phenylacetylglutamine (PAG), trimethylamine-n-oxide (TMAO), and kynurenine-exemplify different mechanisms of clearance. IS and PCS are protein-bound solutes efficiently cleared by the native kidney through tubular secretion. PAG and TMAO are not protein-bound but are also cleared by the native kidney through tubular secretion, while kynurenine is not normally cleared by the kidney. Increases in the plasma levels of the normally secreted solutes IS, PCS, TMAO, and PAG in chronic kidney disease (CKD) are attributable to a reduction in their renal clearances. Levels of each of these potential toxins are even higher in patients on dialysis than in those with advanced chronic kidney disease, which can be accounted for in part by a low ratio of dialytic to native kidney clearance. The rise in plasma kynurenine in CKD and dialysis patients, by contrast, remains to be explained. Our ability to detect lower levels of the potential uremic cardiovascular toxins with renal replacement therapy may be limited by the intermittency of treatment, by increases in solute production, and by the presence of non-renal clearance. Reduction in the levels of uremic cardiovascular toxins may in the future be achieved more effectively by inhibiting their production.


Assuntos
Doenças Cardiovasculares/etiologia , Toxinas Biológicas/metabolismo , Toxinas Biológicas/toxicidade , Uremia , Animais , Humanos , Diálise Renal
9.
J Am Soc Nephrol ; 29(7): 1992-1999, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29728422

RESUMO

Background Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis.Methods We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis.Results Compared with anuric patients on thrice weekly dialysis with the same standard Kt/Vurea, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and p-cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations.Conclusions Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.


Assuntos
Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Diálise Renal/métodos , Idoso , Idoso de 80 Anos ou mais , Cresóis/sangue , Feminino , Glutamina/análogos & derivados , Glutamina/sangue , Hipuratos/sangue , Humanos , Indicã/sangue , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica , Ésteres do Ácido Sulfúrico/sangue , Ureia/sangue
11.
PLoS One ; 12(11): e0188315, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29145509

RESUMO

Many solutes have been reported to remain at higher plasma levels relative to normal than the standard index solute urea in hemodialysis patients. Untargeted mass spectrometry was employed to compare solute levels in plasma and plasma ultrafiltrate of hemodialysis patients and normal subjects. Quantitative assays were employed to check the accuracy of untargeted results for selected solutes and additional measurements were made in dialysate and urine to estimate solute clearances and production. Comparison of peak areas indicated that many solutes accumulated to high levels in hemodialysis patients, with average peak areas in plasma ultrafiltrate of dialysis patients being more than 100 times greater than those in normals for 123 features. Most of these mass spectrometric features were identified only by their mass values. Untargeted analysis correctly ranked the accumulation of 5 solutes which were quantitatively assayed but tended to overestimate its extent. Mathematical modeling showed that the elevation of plasma levels for these solutes could be accounted for by a low dialytic to native kidney clearance ratio and a high dialytic clearance relative to the volume of the accessible compartment. Numerous solutes accumulate to high levels in hemodialysis patients because dialysis does not replicate the clearance provided by the native kidney. Many of these solutes remain to be chemically identified and their pathogenic potential elucidated.


Assuntos
Espectrometria de Massas/métodos , Diálise Renal , Feminino , Humanos , Masculino
12.
Kidney Int ; 92(6): 1484-1492, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28739139

RESUMO

Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders. The mean age of the patients was 58 years, 63% were Black and 42% were male. Overall, there was no association between the solutes and outcomes. However, in sub-group analyses, among patients with lower serum albumin (under 3.6 g/dl), a twofold higher p-cresol sulfate was significantly associated with a 12% higher risk of cardiac death (hazard ratio 1.12; 95% confidence interval, 0.98-1.27) and 22% higher risk of sudden cardiac death (1.22, 1.06-1.41). Similar trends were also noted with indoxyl sulfate. Trial interventions did not modify the association between these solutes and outcomes. Routine clinical and lab data explained less than 22% of the variability in solute levels. Thus, in prevalent hemodialysis patients participating in a large U.S. hemodialysis trial, uremic solutes p-cresol sulfate, indoxyl sulfate, hippurate, and phenylacetylglutamine were not associated with cardiovascular outcomes. However, there were trends of toxicity among patients with lower serum albumin.


Assuntos
Doenças Cardiovasculares/sangue , Cresóis/sangue , Indicã/sangue , Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Ésteres do Ácido Sulfúrico/sangue , Adulto , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Glutamina/análogos & derivados , Glutamina/sangue , Hipuratos/sangue , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Diálise Renal/estatística & dados numéricos , Fatores de Risco , Albumina Sérica/análise , Uremia/sangue , Uremia/complicações
13.
Semin Dial ; 30(5): 403-408, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28558415

RESUMO

More intensive hemodialysis has provided limited clinical benefit. The lack of benefit may be due in part to the failure of intensive dialysis to reduce uremic solute levels in plasma. Two well-described factors limiting the reduction in these levels are the intermittency of dialysis treatment and the distribution of solutes in multiple body compartments. Efforts to increase the clearance of large solutes and protein-bound solutes have revealed two other considerations-the presence of nonrenal clearance and increases in solute generation. For ß2 microglobulin, a commonly measured large solute, nonrenal clearance limits reduction in its levels. For the bound solute p-cresol sulfate, an increase in generation appears to limit its reduction. A variety of factors likely determine the behavior of different solutes. More data on solute toxicity are needed as is better knowledge of solute kinetics. We will then be better able to design optimal therapeutic interventions. A combination of dialytic and nondialytic strategies may well be needed to reduce the plasma levels of toxic solutes and improve patients' health.


Assuntos
Diálise Renal/métodos , Ureia/sangue , Uremia/terapia , Humanos , Cinética
14.
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
15.
Kidney Int ; 91(2): 274-276, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28087007

RESUMO

The application of molecular methods has provided a new picture of the colon microbial flora, or microbiome. The microbiome has been found to be a complex ecosystem with multiple influences on its human host. In renal medicine, interest has focused on the microbiome as a source of toxic waste chemicals and a stimulant to unwanted systemic inflammation. Early attempts to manipulate the microbiome have yielded limited benefit, but further research is strongly motivated.


Assuntos
Microbiota , Humanos
16.
Toxins (Basel) ; 8(12)2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27916890

RESUMO

Indoxyl sulfate is an extensively studied uremic solute. It is a small molecule that is more than 90% bound to plasma proteins. Indoxyl sulfate is derived from the breakdown of tryptophan by colon microbes. The kidneys achieve high clearances of indoxyl sulfate by tubular secretion, a function not replicated by hemodialysis. Clearance by hemodialysis is limited by protein binding since only the free, unbound solute can diffuse across the membrane. Since the dialytic clearance is much lower than the kidney clearance, indoxyl sulfate accumulates to relatively high plasma levels in hemodialysis patients. Indoxyl sulfate has been most frequently implicated as a contributor to renal disease progression and vascular disease. Studies have suggested that indoxyl sulfate also has adverse effects on bones and the central nervous system. The majority of studies have assessed toxicity in cultured cells and animal models. The toxicity in humans has not yet been proven, as most data have been from association studies. Such toxicity data, albeit inconclusive, have prompted efforts to lower the plasma levels of indoxyl sulfate through dialytic and non-dialytic means. The largest randomized trial showed no benefit in renal disease progression with AST-120. No trials have yet tested cardiovascular or mortality benefit. Without such trials, the toxicity of indoxyl sulfate cannot be firmly established.


Assuntos
Indicã/toxicidade , Animais , Doenças Ósseas/metabolismo , Humanos , Nefropatias/metabolismo , Doenças Vasculares/metabolismo
17.
Semin Dial ; 29(6): 481-490, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27556575

RESUMO

Patients maintained on standard three times weekly hemodialysis have a high mortality rate and a limited quality of life. Some of this illness is due to systemic diseases that have caused kidney failure, and thus may be irreversible. But we presume that imperfect replacement of normal kidney function by dialysis contributes importantly. Patients on hemodialysis are subject to fluctuations in extracellular fluid volume and inorganic ion concentrations and their plasma levels of many organic waste solutes remain very high. It is thus natural to suppose that their health could be improved by increasing the intensity of dialysis treatment. But despite a great deal of work over the past 20 years, evidence that such improvement can be obtained is generally lacking. Specific benefits can indeed be achieved. Patients who cannot control their intradialytic weight gains or plasma phosphate levels with standard therapy can benefit from extending treatment time. But we cannot promise the average patient that longer or more frequent treatment will reduce mortality or improve the quality of life.


Assuntos
Falência Renal Crônica/terapia , Nefrologia/tendências , Diálise Renal , Humanos , Falência Renal Crônica/mortalidade , Fosfatos/sangue , Qualidade de Vida , Ganho de Peso
18.
J Am Soc Nephrol ; 27(12): 3780-3787, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27444566

RESUMO

Retention of uremic metabolites is a proposed cause of cognitive impairment in patients with ESRD. We used metabolic profiling to identify and validate uremic metabolites associated with impairment in executive function in two cohorts of patients receiving maintenance dialysis. We performed metabolic profiling using liquid chromatography/mass spectrometry applied to predialysis plasma samples from a discovery cohort of 141 patients and an independent replication cohort of 180 patients participating in a trial of frequent hemodialysis. We assessed executive function with the Trail Making Test Part B and the Digit Symbol Substitution test. Impaired executive function was defined as a score ≥2 SDs below normative values. Four metabolites-4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline-were associated with impaired executive function at the false-detection rate significance threshold. After adjustment for demographic and clinical characteristics, the associations remained statistically significant: relative risk 1.16 (95% confidence interval [95% CI], 1.03 to 1.32), 1.39 (95% CI, 1.13 to 1.71), 1.24 (95% CI, 1.03 to 1.50), and 1.20 (95% CI, 1.05 to 1.38) for each SD increase in 4-hydroxyphenylacetate, phenylacetylglutamine, hippurate, and prolyl-hydroxyproline, respectively. The association between 4-hydroxyphenylacetate and impaired executive function was replicated in the second cohort (relative risk 1.12; 95% CI, 1.02 to 1.23), whereas the associations for phenylacetylglutamine, hippurate, and prolyl-hydroxyproline did not reach statistical significance in this cohort. In summary, four metabolites related to phenylalanine, benzoate, and glutamate metabolism may be markers of cognitive impairment in patients receiving maintenance dialysis.


Assuntos
Transtornos Cognitivos/metabolismo , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Diálise Renal , Transtornos Cognitivos/etiologia , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Metabolômica , Pessoa de Meia-Idade
19.
Nephrol Dial Transplant ; 31(8): 1335-41, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27190347

RESUMO

BACKGROUND: The protein-bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate to high plasma levels in renal failure and have been associated with adverse events. The clearance of these bound solutes can be altered independently of the urea clearance by changing the dialysate flow and dialyzer size. This study tested whether a sustained difference in clearance would change the plasma levels of PCS and IS. METHODS: Fourteen patients on thrice-weekly nocturnal hemodialysis completed a crossover study of two periods designed to achieve widely different bound solute clearances. We compared the changes in pre-dialysis plasma PCS and IS levels from baseline over the course of the two periods. RESULTS: The high-clearance period provided much higher PCS and IS clearances than the low-clearance period (PCS: 23 ± 4 mL/min versus 12 ± 3 mL/min, P < 0.001; IS: 30 ± 5 mL/min versus 17 ± 4 mL/min, P < 0.001). Despite the large difference in clearance, the high-clearance period did not have a different effect on PCS levels than the low-clearance period [from baseline, high: +11% (-5, +37) versus low: -8% (-18, +32), (median, 25th, 75th percentile), P = 0.50]. In contrast, the high-clearance period significantly lowered IS levels compared with the low-clearance period [from baseline, high: -4% (-17, +1) versus low: +22% (+14, +31), P < 0.001). The amount of PCS removed in the dialysate was significantly greater at the end of the high-clearance period [269 (206, 312) versus 199 (111, 232) mg per treatment, P < 0.001], while the amount of IS removed was not different [140 (87, 196) versus 116 (89, 170) mg per treatment, P = 0.15]. CONCLUSIONS: These findings suggest that an increase in PCS generation prevents plasma levels from falling when the dialytic clearance is increased. Suppression of solute generation may be required to reduce plasma PCS levels in dialysis patients.


Assuntos
Cresóis/sangue , Soluções para Diálise/farmacocinética , Indicã/sangue , Diálise Renal/métodos , Insuficiência Renal/terapia , Ésteres do Ácido Sulfúrico/sangue , Biomarcadores/sangue , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/sangue
20.
J Am Soc Nephrol ; 27(11): 3469-3478, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27026365

RESUMO

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/Vurea of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/Vurea of 1.32. Here, we assessed whether the high-dose treatment used lowered plasma levels of small uremic solutes other than urea. Measurements made ≥3 months after randomization in 1281 patients in the HEMO Study showed a range in the effect of high-dose treatment compared with that of standard treatment: from no reduction in the level of p-cresol sulfate or asymmetric dimethylarginine to significant reductions in the levels of trimethylamine oxide (-9%; 95% confidence interval [95% CI], -2% to -15%), indoxyl sulfate (-11%; 95% CI, -6% to -15%), and methylguanidine (-22%; 95% CI, -18% to -27%). Levels of three other small solutes also decreased slightly; the level of urea decreased 9%. All-cause mortality did not significantly relate to the level of any of the solutes measured. Modeling indicated that the intermittency of treatment along with the presence of nondialytic clearance and/or increased solute production accounted for the limited reduction in solute levels with the higher Kt/Vurea In conclusion, failure to achieve greater reductions in solute levels may explain the failure of high Kt/Vurea treatment to improve outcomes in the HEMO Study. Furthermore, levels of the nonurea solutes varied widely among patients in the HEMO Study, and achieved Kt/Vurea accounted for very little of this variation. These results further suggest that an index only on the basis of urea does not provide a sufficient measure of dialysis adequacy.


Assuntos
Diálise Renal , Ureia/metabolismo , Feminino , Soluções para Hemodiálise/química , Humanos , Masculino , Pessoa de Meia-Idade , Ureia/análise
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