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Biomedical subjects

Salim Mujais

Publications and source records attributed to Salim Mujais.

At least 19 recordsLinked to original sources

Health-related quality of life predicts outcomes but is not affected by peritoneal clearance: The ADEMEX trial.

BACKGROUND: We hypothesized that increasing small solute clearance in peritoneal dialysis (PD) would lead to improvements in patient health-related quality of life (HRQOL). METHODS: Patients were randomized to a control group [standard 4 x 2 L continuous ambulatory peritoneal dialysis (CAPD)] and an intervention group (CAPD with a target creatinine clearance >/=60 L/week/1.73 m(2)). The Kidney Disease Quality of Life Short Form was obtained at baseline and at 6, 12, and 24 months. Physical (PCS), mental (MCS), and kidney disease component summary (KDCS) scores were computed. RESULTS: The two groups were comparable at baseline with respect to HRQOL. Baseline variables highly predictive of better QOL included absence of diabetes, younger age, higher starting GFR, and serum albumin. Baseline values of QOL were highly predictive of survival and hospitalizations. An unadjusted comparison revealed that patients in the intervention group had significantly higher PCS and KDCS scores at six months. However, there were no significant differences between the intervention and control patients at 12 or 24 months. When similar analyses were carried out adjusting for different patterns of patient dropout, there were no significant differences between the two groups at any time point in terms of PCS, MCS, and KDCS scores. CONCLUSION: We found no evidence of a long-term benefit in HRQOL of CAPD patients by increasing peritoneal small-solute clearances when HRQOL parameters were adjusted for patient dropout. Measures of HRQOL have a significant predictive value for patient survival and hospitalizations.

Adult↗

Impact of initial dialysis modality and modality switches on Medicare expenditures of end-stage renal disease patients.

BACKGROUND: The number of end-stage renal disease (ESRD) enrollees and Medicare expenditures have increased dramatically. Pathways and associated Medicare expenditures in ESRD treatment need to be examined to potentially improve the efficiency of care. METHODS: This study examines the impact of initial dialysis modality choice and subsequent modality switches on Medicare expenditure in a 3-year period. The Dialysis Morbidity and Mortality Study Wave 2 data by the United States Renal Data System (USRDS) is used along with the USRDS Core CD and USRDS claims data. RESULTS: A total of 3423 incident dialysis patients (approximately equal number of peritoneal dialysis and hemodialysis) were included in the analysis. Unadjusted average annual Medicare expenditure (in 2004 dollars) for peritoneal dialysis as first modality was 53,277 dollars(95% CI 50,626 dollars-55,927 dollars), and 72,189 dollars (95% CI 67,513 dollars-76,865 dollars) for hemodialysis. Compared to "hemodialysis, no switch" subgroup, "peritoneal dialysis, no switch" had a significantly lower annual expenditure (44,111 dollars vs. 72,185 dollars) (P < 0.001). "Peritoneal dialysis, with at least one switch" and "hemodialysis, with at least one switch" had a lower or similar annual expenditure of 66,639 dollars and 72,335 dollars, respectively. After adjusting for patient characteristics, annual Medicare expenditure was still significantly lower for patients with peritoneal dialysis as the initial modality (56,807 dollars vs. 68,253 dollars) (P < 0.001). Similarly, compared to "hemdialysis, no switch" subgroup, "peritoneal dialysis, no switch" and "peritoneal dialysis, with at least one switch" had a significantly lower total expenditure. Further analysis showed that time-to-first switch also independently impacted total expenditure. CONCLUSION: Initial modality choice (peritoneal dialysis or hemodialysis) and subsequent modality switches had significant implications for Medicare expenditure on ESRD treatments.

Adult↗

Superiority of icodextrin compared with 4.25% dextrose for peritoneal ultrafiltration.

Several clinical observations suggest the superiority of icodextrin compared with 4.25% dextrose in optimizing peritoneal ultrafiltration (UF), but no rigorous controlled evaluation has hitherto been performed. For comparing icodextrin and 4.25% dextrose during the long dwell of automated peritoneal dialysis, a multicenter, randomized, double-blind trial was conducted in 92 patients (control, 45; icodextrin, 47) with 4-h dialysate to plasma ratio creatinine >0.70 and D/D(0) glucose <0.34. Long-dwell net UF and the UF efficiency ratio (net UF volume per gram of dialysate carbohydrate absorbed) were determined at baseline, week 1, and week 2. The control and treatment groups were comparable at baseline (all patients using 4.25% dextrose for the long dwell) with regard to mean (+/-SEM) net UF (201.7 +/- 103.1 versus 141.6 +/- 75.4 ml, respectively; P = 0.637) and the percentage of patients with negative net UF (control, 37.8%; treatment, 42.6%; P = 0.641). During the study period, net UF was unchanged from baseline in the control group but increased significantly (P < 0.001) in the icodextrin group from 141.6 +/- 75.4 to 505.8 +/- 46.8 ml at week 1 and 540.2 +/- 46.8 ml at week 2. In the icodextrin group, the incidence of negative net UF was significantly lower (P < 0.0001) than in the control group. Findings were similar for UF efficiency ratio. Rash was reported significantly more often in the icodextrin group. This study showed that in high-average and high transporters, icodextrin is superior to 4.25% dextrose for long-dwell fluid and solute removal.

Dialysis Solutions↗

Patient and technique survival on peritoneal dialysis in the United States: evaluation in large incident cohorts.

Patient and technique survival on peritoneal dialysis in the United States: Evaluation in large incident cohorts. Secular trends in dialysis require a frequent re-examination of outcomes in patients on renal replacement modalities. We examined three large cohorts of patients initiating peritoneal dialysis (PD) in 1999, 2000, and 2001 (total of > 30,000 patients) to ascertain trends in patient outcomes, technique success, and predictors of both parameters of interest. Trends toward improved patient survival, higher technique success, and increasing use of cycler-based therapy, with more recent calendar years were noted. Age and diabetes were clear predictors of patient survival, but did not appear to influence technique success. Technique success was higher in patients on automated PD (APD) than in patients on continuous ambulatory PD (CAPD), but this difference was mostly concentrated in the first year on therapy. Patients starting PD after a failed allograft had excellent survival. We conclude that the current state of PD in the United States is characterized by improving patient outcomes, higher technique success, and a predominance of use of cycler-based therapy. Several opportunities for improving technique success amenable to practice interventions have been identified. The high success of PD in patients with failed allograft suggests that it is beneficial to utilize this modality more frequently in this patient group than current practice.

Automation↗

Acid-base profile in patients on PD.

Acid-base profile in patients on PD. Secular trends in dialysis dose in peritoneal dialysis (PD) and modes of dialysis delivery [automated PD (APD) versus continuous ambulatory PD (CAPD)] require a reexamination of acid-base status in patients treated with these renal replacement modalities. We explored steady-state acid-base profile and its determinants in 175 patients on CAPD and 77 patients on APD. The majority (62% to 70%) of patients had serum bicarbonate levels in the normal range, and a minority (17% to 27%) had values just above 28 mEq/L. Only a small percentage (10% to 12%) of patients in either the CAPD or the APD groups had a serum HCO3 less than 22 mEq/L, an indication of the successful correction of acidosis in most patients. The anion gap was elevated (> 16 mEq/L) in the majority of patients on CAPD and APD and bore an inverse relationship to serum HCO3 and a direct relationship to serum albumin and serum phosphate. In CAPD patients, but not APD patients, a significant inverse relationship was observed between the anion gap and peritoneal permeability as assessed by four-hour D/P(creatinine). The correction of acidosis in PD appears to be predominantly achieved by the continuous supplementation of alkali via dialysis, with residual renal function not differentiating the degree of correction. Steady-state serum bicarbonate in patients on CAPD appeared to be responsive to the underlying peritoneal membrane permeability characteristics of the patient that govern alkali loss and gain, but the higher dialysate volumes in APD appear to override this effect. Higher albumin, blood urea nitrogen (BUN), and phosphate in patients with lower HCO3 suggest a discrepancy between daily acid load and dialysis dose.

Acid-Base Equilibrium↗

Buffer transport in peritoneal dialysis.

Buffer transport in peritoneal dialysis. The success of peritoneal dialysis as a robust modality of renal replacement therapy has invited a quest for ameliorations in its underlying technology aimed at enhancing patient satisfaction and preserving the central instrument of the therapy, namely the peritoneal membrane. The health and longevity of the membrane have motivated and continue to drive a series of iterative innovations in the composition, methods of production, and delivery of dialysis solutions. It is the purpose of this article to review aspects of these innovations pertaining to buffer composition in dialysis solutions and the peritoneal mechanisms of buffer transport.

Biological Transport↗

The uremic syndrome: therapeutic-evaluative discordance.

Significant discordances are observed between the therapeutic needs of patients with end-stage renal disease and the current emphasis in renal science and technologies. These discordances manifest in the observation that renal replacement therapies fail to attenuate the impact of the patient status at the time of initiation of renal replacement on mortality and morbidity; in the failure to apply a rigorous approach for fluid management, despite its technical simplicity; in the inadequacy of dialysis in the correction of deficient excretion of some solutes (phosphate and potassium), and in the greater impact of hormonal replacement on outcome than that observed by dialytic techniques. We suggest that these discordances find their root in the limited spectrum of uremic solute removal that is currently available with various dialytic techniques, and we suggest that a re-examination of the therapeutic targets in dialytic therapy may be needed in order to supercede the therapeutic plateau at which the therapy is currently fixed.

Humans↗

Pharmacokinetics of icodextrin in peritoneal dialysis patients.

UNLABELLED: Pharmacokinetics of icodextrin in peritoneal dialysis patients. BACKGROUND: Icodextrin is a glucose polymer osmotic agent used to provide sustained ultrafiltration during long peritoneal dialysis (PD) dwells. A number of studies have evaluated the steady-state blood concentrations of icodextrin during repeated use; however, to date the pharmacokinetics of icodextrin have not been well studied. The current study was conducted to determine the absorption, plasma kinetics and elimination of icodextrin and metabolites following a single icodextrin exchange. METHODS: Thirteen PD patients were administered 2.0 L of solution containing 7.5% icodextrin for a 12-hour dwell. Icodextrin (total of all glucose polymers) and specific polymers with degrees of polymerization ranging from two to seven (DP2 to DP7) were measured in blood, urine and dialysate during the dwell and after draining the solution from the peritoneal cavity. RESULTS: A median of 40.1% (60.24 g) of the total administered dose (150 g) was absorbed during the 12-hour dwell. Plasma levels of icodextrin and metabolites rose during the dwell and declined after drain, closely corresponding to the one-compartment pharmacokinetic model assuming zero-order absorption and first-order elimination. Peak plasma concentrations (median C peak = 2.23 g/L) were observed at the end of the dwell (median Tmax = 12.7 h) and were significantly correlated with patients' body weight (R2 = 0.805, P < 0.001). Plasma levels of icodextrin and metabolites returned to baseline within 3 to 7 days. Icodextrin had a plasma half-life of 14.73 hours and a median clearance of 1.09 L/h. Urinary excretion of icodextrin and metabolites was directly related to residual renal function (R2 = 0.679 vs. creatinine clearance, P < 0.01). In the nine patients with residual renal function, the average daily urinary excretion of icodextrin was 473 +/- 77 mg per mL of endogenous renal creatinine clearance. Icodextrin metabolites DP2 to DP4 were found in the dialysate of subsequent dextrose exchanges, contributing to their elimination from blood. Changes in intraperitoneal concentrations of icodextrin metabolites during the dwell revealed a dual pattern, with a progressive rise in the dialysate concentration of smaller polymers (DP2 to DP4) and a progressive decline in the dialysate concentrations of the larger polymers (DP5 to DP7), suggesting some intraperitoneal metabolism of the glucose polymers. This increase in dialysate metabolite levels, however, did not contribute significantly to dialysate osmolality. In addition, some diffusion of maltose (DP2) from blood to dialysate may have occurred. There were no changes in serum insulin or glucose levels during icodextrin administration, indicating that icodextrin does not result in hyperglycemia or hyperinsulinemia as occurs during dextrose-based dialysis. Serum sodium and chloride declined in parallel with the rise in plasma levels of icodextrin, supporting the hypothesis that these electrolyte changes are the result of the increased plasma osmolality due to the presence of icodextrin metabolites. CONCLUSIONS: The pharmacokinetics of icodextrin in blood following intraperitoneal administration conforms to a simple, single-compartment model that can be approximated by zero-order absorption and first-order elimination. A small amount of intraperitoneal metabolism of icodextrin occurs but does not contribute significantly to dialysate osmolality. The metabolism of absorbed icodextrin and the resultant rise in plasma levels of small glucose polymers (DP2 to DP4) do not result in hyperglycemia or hyperinsulinemia, but may result in a small decrease in serum sodium and chloride.

Absorption↗

Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial.

Small-solute clearance targets for peritoneal dialysis (PD) have been based on the tacit assumption that peritoneal and renal clearances are equivalent and therefore additive. Although several studies have established that patient survival is directly correlated with renal clearances, there have been no randomized, controlled, interventional trials examining the effects of increases in peritoneal small-solute clearances on patient survival. A prospective, randomized, controlled, clinical trial was performed to study the effects of increased peritoneal small-solute clearances on clinical outcomes among patients with end-stage renal disease who were being treated with PD. A total of 965 subjects were randomly assigned to the intervention or control group (in a 1:1 ratio). Subjects in the control group continued to receive their preexisting PD prescriptions, which consisted of four daily exchanges with 2 L of standard PD solution. The subjects in the intervention group were treated with a modified prescription, to achieve a peritoneal creatinine clearance (pCrCl) of 60 L/wk per 1.73 m(2). The primary endpoint was death. The minimal follow-up period was 2 yr. The study groups were similar with respect to demographic characteristics, causes of renal disease, prevalence of coexisting conditions, residual renal function, peritoneal clearances before intervention, hematocrit values, and multiple indicators of nutritional status. In the control group, peritoneal creatinine clearance (pCrCl) and peritoneal urea clearance (Kt/V) values remained constant for the duration of the study. In the intervention group, pCrCl and peritoneal Kt/V values predictably increased and remained separated from the values for the control group for the entire duration of the study (P < 0.01). Patient survival was similar for the control and intervention groups in an intent-to-treat analysis, with a relative risk of death (intervention/control) of 1.00 [95% confidence interval (CI), 0.80 to 1.24]. Overall, the control group exhibited a 1-yr survival of 85.5% (CI, 82.2 to 88.7%) and a 2-yr survival of 68.3% (CI, 64.2 to 72.9%). Similarly, the intervention group exhibited a 1-yr survival of 83.9% (CI, 80.6 to 87.2%) and a 2-yr survival of 69.3% (CI, 65.1 to 73.6%). An as-treated analysis revealed similar results (overall relative risk = 0.93; CI, 0.71 to 1.22; P = 0.6121). Mortality rates for the two groups remained similar even after adjustment for factors known to be associated with survival for patients undergoing PD (e.g., age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria). This study provides evidence that increases in peritoneal small-solute clearances within the range studied have a neutral effect on patient survival, even when the groups are stratified according to a variety of factors (age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria) known to affect survival. No clear survival advantage was obtained with increases in peritoneal small-solute clearances within the range achieved in this study.

Analysis of Variance↗

Impact of fill volume on peritoneal clearances and cytokine appearance in peritoneal dialysis.

BACKGROUND: Current adequacy guidelines for peritoneal dialysis encourage the use of large fill volumes for the attainment of small solute clearance targets. These guidelines have influenced clinical practice in a significant way, and adoption of higher fill volumes has become common in North America. Several studies, however, have challenged the relevance of increasing small solute clearance; this practice may result in untoward consequences in patients. OBJECTIVE: The present study was designed to explore the relationship between dialysate volume and the clearance of different sized molecules, fluid dynamics, and appearance of peritoneal cytokines. METHODS: Thirteen adult prevalent patients on continuous ambulatory peritoneal dialysis were studied. Three different dialysate volumes (2.0, 2.5, and 3.0 L) were infused on consecutive days in a random order. Several measurements of peritoneal fluid dynamics (intraperitoneal pressure, net ultrafiltration, fluid absorption), solute clearances (urea, creatinine, beta2-microglobulin, albumin, IgG, and transferrin), and appearance of interleukin-6 and tumor necrosis factor alpha (TNFalpha) were assessed. RESULTS: Increase in dialysate fill volume (from 2 to 2.5 to 3 L) was examined in relationship to body surface area (BSA). The dialysate volume/BSA (DV/BSA) ratio increased from 1262 to 1566 to 1871 mL/m2 on 2.0, 2.5, and 3.0 L dialysate volumes, respectively. In parallel, diastolic blood pressure increased from 82.7 +/- 8.8 to 87.0 +/- 9.5 to 92 +/- 8.3 mmHg (p < 0.05). Net ultrafiltration rate also increased, from 0.46 +/- 0.48 to 0.72 +/- 0.42 to 0.97 +/- 0.49 mL/minute (p < 0.01), despite a concomitant increase in fluid absorption, from 1.05 +/- 0.34 to 1.21 +/- 0.40 to 1.56 +/- 0.22 mL/min (p < 0.01). Urea peritoneal clearance increased from 8.27 +/- 0.68 to 9.92 +/- 1.6 to 12.98 +/- 4.03 mL/min (p < 0.01); creatinine peritoneal clearance increased from 6.69 +/- 1.01 to 7.64 +/- 1.12 to 8.69 +/- 1.76 mL/min (p < 0.01). Clearance of the other measured molecules did not change. Appearance of interleukin-6 increased 17% and 43% (p < 0.01), and TNFalpha appearance increased 14% and 50% (p < 0.01) when dialysate volumes of 2.5 and 3.0 L were used, compared with 2.0 L. CONCLUSIONS: These results show that, with higher values of DV/BSA ratio, small solute peritoneal clearance is increased, but clearances of large molecules remain unchanged. With the use of higher volumes, fluid absorption rate and the appearance of proinflammatory cytokines in the dialysate are increased.

Absorption↗