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Biomedical subjects

Marcello Tonelli

Publications and source records attributed to Marcello Tonelli.

14 recordsLinked to original sources
PubMed2003

Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency.

BACKGROUND: Cardiovascular disease is a common cause of morbidity and death in persons with renal insufficiency. Although 3-hydroxy-3methylglutaryl coenzyme A reductase inhibitors (statins) are effective for secondary prevention of cardiovascular events in the general population, they have not been specifically studied in chronic renal insufficiency. OBJECTIVE: To determine whether pravastatin is effective and safe for secondary prevention of cardiovascular events in persons with chronic renal insufficiency. DESIGN: Post hoc subgroup analysis of a randomized, double-blind, placebo-controlled trial. SETTING: The Cholesterol and Recurrent Events (CARE) study, a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol levels less than 6.21 mmol/L (<240 mg/dL). PARTICIPANTS: 1711 participants with chronic renal insufficiency defined by creatinine clearance less than or equal to 75 mL/min, using the Cockcroft-Gault equation. MEASUREMENTS: The primary outcome was death from coronary disease or symptomatic nonfatal myocardial infarction. RESULTS: After a median follow-up of 58.9 months, the incidence of the primary end point was lower in participants receiving pravastatin than in those receiving placebo (adjusted hazard ratio, 0.72 [95% CI, 0.55 to 0.95]; P = 0.02). Pravastatin was associated with lower adjusted hazard ratios for major coronary events (0.72 [CI, 0.59 to 0.88]; P = 0.001) and coronary revascularization (0.65 [CI, 0.50 to 0.83]; P = 0.001), but not total mortality (0.81 [CI, 0.61 to 1.08]; P = 0.14) or stroke (0.62 [CI, 0.39 to 1.00]; P = 0.051). Tests for interaction suggested that the observed benefit was independent of the presence and severity of renal insufficiency. Incidence of side effects was similar in persons receiving pravastatin and those receiving placebo. CONCLUSIONS: These data suggest that pravastatin is effective and appears safe for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Since statins may be underused in this setting, physicians should consider prescribing them for patients with chronic renal insufficiency and known coronary disease.

Aged↗
PubMed2003

The cost-effectiveness of maintaining higher hemoglobin targets with erythropoietin in hemodialysis patients.

BACKGROUND: There is uncertainty regarding the appropriate target hemoglobin level in hemodialysis patients treated with erythropoietin (EPO). METHODS: We sought to determine the incremental cost-effectiveness of prescribing EPO to maintain different target hemoglobin levels, by incorporating the impact of EPO on health-related quality-of-life (HRQOL) issues and adopting the perspective of the health care purchaser. We evaluated the prescription of EPO to maintain target hemoglobin levels of 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, compared with 9.5 to 10.5 g/dL. Model outputs were quality-adjusted life expectancy and costs. RESULTS: The base case analysis estimated intravenous EPO requirements to be 3523, 5078, 6097, and 9341 units three times per week to maintain targets of 9.5 to 10.5, 11.0 to 12.0, 12.0 to 12.5, and 14.0 g/dL, respectively. The cost per quality-adjusted life year (QALY) gained for the 11.0 to 12.0 g/dL target vs. 9.5 to 10.5 g/dL was $55,295 US. For the 12.0 to 12.5 g/dL target compared to 11.0 to 12.0 g/dL, and 14.0 g/dL target compared to 12.0 to 12.5 g/dL, the costs per QALY gained were $613,015 US and $828,215 US, respectively. In sensitivity analysis, clinically implausible reductions in hospitalization or EPO requirements associated with the two higher hemoglobin targets were required to make their incremental cost per QALY gained <$100,000 US. CONCLUSION: Dosing intravenous EPO to achieve hemoglobin targets of 11.0 to 12.0 g/dL appears to be associated with incremental cost per QALY gained of $50,000 to $60,000, compared with a hemoglobin target of 9.5 to 10.5 g/dL. Aiming for hemoglobin targets in excess of 12.0 g/dL is associated with unfavorable cost-effectiveness ratios and should not be undertaken based on current data.

Cost-Benefit Analysis↗
PubMed2003

Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease.

Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency. This was a post hoc subgroup analysis of a randomized double-blind placebo controlled trial. Data were analyzed from the CARE study (a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol < 240 mg/dl). Participants with estimated GFR (MDRD-GFR) < 60 ml/min per 1.73 m(2) body surface area at baseline were considered to have moderate chronic renal insufficiency. Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo, controlling for prospectively determined covariates that might influence rates of renal function loss. Change in renal function could be calculated in 3384 individuals, of whom 690 (20.4%) had MDRD-GFR < 60 ml/min per 1.73 m(2) and were eligible for inclusion. Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2)), the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group (0.1 ml/min per 1.73 m(2)/yr slower; 95% CI, -0.2 to 0.4; P = 0.49). However, there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower MDRD-GFR at baseline (P = 0.04). Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo (95% CI, -0.1 to 1.2; P = 0.07) in those with MDRD-GFR < 50 ml/min, and 2.5 ml/min per 1.73 m(2)/yr slower (95% CI, 1.4 to 3.6 slower; P = 0.0001) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr. Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline (P = 0.006). It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency.

Aged↗
PubMed2003

The change in allograft function among long-term kidney transplant recipients.

Long-term kidney allograft survival continues to remain an elusive goal. Kidney transplant recipients are believed to be at high risk for loss of allograft function, and new, potentially non-nephrotoxic immunosuppressive medications are advocated to improve long-term allograft survival. To evaluate the efficacy of such therapeutic interventions, information regarding the change in GFR among kidney transplant recipients with long-term allograft survival is needed. We studied 40,963 transplant recipients between 1987 and 1996 with allograft survival of at least 2 yr in the United States Renal Data System. Linear regression methods were applied to serial GFR estimates after transplantation. The baseline mean GFR at 6 mo after transplantation was 49.6 +/- 15.4 ml/min per 1.73 m(2). During the mean follow-up of 5.7 +/- 2.3 yr, the mean +/- standard error of the change in GFR was -1.66 +/- 6.51 ml/min per 1.73 m(2) per year (median, -0.94 L/min per 1.73 m(2) per year). A total of 12,583 (30%) of patients had improvement in GFR, 8133 (20%) patients had no change in GFR, and 20,247 (50%) patients had decline in GFR. It is concluded that, although most patients had significant impairment of GFR at baseline, the decline in GFR was slow and many patients had either no change or improvement in GFR. Strategies to improve long-term kidney allograft survival that increase baseline allograft function may be more effective than strategies to slow the decline in GFR.

Adult↗
PubMed2003

Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery.

OBJECTIVE: Acute renal failure can be treated with continuous renal replacement therapy (CRRT) or intermittent hemodialysis. There is no difference in mortality, although patients treated with CRRT may have a higher rate of renal recovery. Given these considerations, an estimate of the costs by modality may help in choosing the method of dialysis. As such, the objective of this study was to estimate the cost of CRRT and intermittent hemodialysis in the intensive care unit and to explore the impact of renal recovery on subsequent clinical outcomes and costs among survivors. DESIGN: Retrospective cohort study of all patients who developed acute renal failure and required dialysis between April 1, 1996, and March 31, 1999. SETTING: Two tertiary care intensive care units in Calgary, Canada. PATIENTS: A total of 261 critically ill patients. INTERVENTIONS: None. MEASUREMENTS: All patients were followed to determine in-hospital and subsequent clinical outcomes (survival and frequency of renal recovery). The immediate and potential long-term costs of CRRT and intermittent hemodialysis were measured. MAIN RESULTS: The cost of performing CRRT ranged from Can 3,486 dollars to Can 5,117 dollars per week, depending on the modality and the anticoagulant used, and it was significantly more expensive than intermittent hemodialysis (Can 1,342 dollars per week). Survivors with renal recovery spent significantly fewer days in hospital (11.3 vs. 22.5 days, p<.001) and incurred less healthcare costs (11,192 dollars vs. 73,273 dollars, p<.001) over the year after hospital discharge compared with survivors who remained on dialysis. CONCLUSIONS: Immediate cost savings could be achieved by increasing the use of intermittent hemodialysis rather than CRRT for patients with acute renal failure in the intensive care unit. Because of the high cost of ongoing dialysis, CRRT may still be an economically efficient treatment if it improves renal recovery among survivors; further study in this area is required.

Acute Kidney Injury↗
PubMed2002

Patients with Fabry disease on dialysis in the United States.

BACKGROUND: : Fabry disease results from an X-linked deficiency of lysosomal alpha-galactosidase A and is a rare cause of end-stage renal disease. Little is known about the characteristics of patients with Fabry disease that initiate dialysis in the United States, although data from Europe suggests these individuals have a poor survival. METHODS: : Using the United States Renal Disease System database, we first studied in detail 42 Fabry patients who initiated dialysis between April 1995 (following the introduction of the new detailed HCFA 2728 form) and July 1998. To examine crude survival in a larger cohort, 95 Fabry patients were studied who initiated dialysis between 1985 and 1993, similar to the European Registry. Diabetic and non-diabetic controls matched by age, gender, race, year of dialysis initiation, and initial dialysis modality were examined for comparison. RESULTS: : During the years 1995 to 1998, the mean age of Fabry patients that initiated dialysis was 42 years, 83% were Caucasian, and 10% were African American. Despite the X-linked inheritance of Fabry disease, 12% of Fabry patients on dialysis were female. At initiation of dialysis mean serum albumin and creatinine were significantly higher and mean body mass index was significantly lower among Fabry patients, but mean glomerular filtration rate was similar to controls. Fabry patients tended to have a lower three-year survival compared to non-diabetic controls, but the results were not significantly different. In a larger cohort of Fabry patients who initiated dialysis between 1985 and 1993, the three-year survival of Fabry patients was significantly lower than non-diabetic controls: 63% (95% CI, 50 to 75%) versus 74% (95% CI, 67 to 80%; P=0.03). CONCLUSION: : End-stage renal disease is associated with significant morbidity and mortality among patients with Fabry disease. Recent evidence that progression of Fabry disease may be attenuated by enzyme replacement therapy necessitates increased awareness of Fabry disease and its comorbidities.

Adult↗
PubMed2002

Blood volume monitoring in intermittent hemodialysis for acute renal failure.

BACKGROUND: Although hypotension commonly accompanies intermittent hemodialysis for acute renal failure (ARF) in the intensive care unit (ICU), little is known about how it may be prevented. Online relative blood volume (RBV) monitoring has been used to reduce hypotension in chronic hemodialysis, but is of unproven benefit in ARF. This study tested the hypothesis that hypotension is predictable using online RBV monitoring in patients dialyzed for ARF in an ICU setting. METHODS: The primary definition of hypotension was mean arterial pressure (MAP) <70 mm Hg; systolic blood pressure (SBP) <100 mm Hg was used as a secondary outcome. Fifty-seven treatments were prospectively studied in twenty consecutive adult patients treated with intermittent hemodialysis. RBV was continuously measured using the Hemoscan device (Gambro). RESULTS: Hypotension occurred in 30% of treatments as defined by MAP, and 18% as defined by SBP. There was no evidence of patient-specific or universal RBV thresholds that were associated with hypotension. Analysis using the kappa statistic showed that concordance of RBV and hypotension (that is, RBV falling prior to hypotensive episodes rather than rising or remaining stable) was no greater than chance. RBV and rate of change in RBV slopes did not predict hypotension as a dichotomous outcome, and were not correlated with MAP or SBP whether autocorrelation was corrected for or neglected. Substituting rate of change in RBV (RBV slopes) for absolute RBV values did not improve predictive power. CONCLUSIONS: These results suggest that strategies based on online RBV monitoring are unlikely to reduce hypotension in intermittent hemodialysis for ARF that is delivered through central venous catheters.

Acute Kidney Injury↗
PubMed2002

Acute renal failure in the intensive care unit: a systematic review of the impact of dialytic modality on mortality and renal recovery.

BACKGROUND: There is controversy about which dialytic modality should be used for the treatment of acute renal failure (ARF) in the intensive care unit. We performed a systematic review and meta-analysis to determine the relative risks (RRs) of mortality and renal recovery associated with intermittent hemodialysis (IHD) therapy compared with continuous renal replacement therapy (CRRT) in critically ill adults with ARF. METHODS: Four databases (MEDLINE, Cochrane Library, Database of Abstracts and Reviews, and Science Citation Index), hand searching of conference proceedings and journals, manual review of bibliographies from identified articles, and contact with experts were used. All randomized trials (published or unpublished in any language) that compared mortality between intermittent and continuous treatments were eligible. Trials for which an RR for mortality could not be calculated or with multiple experimental interventions were excluded. Data were extracted separately by two authors and recorded on a standardized form. Disagreements were resolved by consensus. RESULTS: Six eligible trials were identified; four of these provided data on renal outcomes. RR (mortality) for IHD was 0.96 (95% confidence interval [CI], 0.85 to 1.08; P = 0.50), RR (renal death) was 1.02 (95% CI, 0.89 to 1.17; P = 0.78), and RR (dialysis dependence) in survivors was 1.19 (95% CI, 0.62 to 2.27; P = 0.60; all compared with continuous therapy). Several sensitivity analyses did not change these results. Of the outcomes studied, the risk for dialysis dependence in survivors would be most sensitive to the addition of new trials. CONCLUSIONS: In comparison to IHD therapy, CRRT does not improve survival or renal recovery in unselected critically ill patients with ARF. Future studies should focus on well-defined subgroups of such patients using lessons learned from the trials in this meta-analysis. The high cost of chronic dialysis therapy and the relative instability of the RR for dialysis dependence suggest that future trials also should evaluate differences in renal recovery between dialytic modalities.

APACHE↗
PubMed2002

Barriers to blood pressure control and angiotensin enzyme inhibitor use in Canadian patients with chronic renal insufficiency.

BACKGROUND: Current recommendations for the management of chronic renal insufficiency (CRI) include the use of angiotensin-converting enzyme inhibitors (ACEI) and achieving target blood pressure control. We designed this study to describe the use of these therapeutic strategies, and to investigate barriers to their implementation. METHODS: This was a prospective study of 304 consecutive CRI patients, seen at follow-up in four nephrology clinics across Canada. The use of blood pressure control and antihypertensive medication (AHM) in each of these clinics was recorded, and a questionnaire was administered to nephrologists to determine the basis for decisions concerning AHM regimens and ACEI use/non-use. RESULTS: Mean age was 60.8+/-15.7 years, mean creatinine clearance was 30.3+/-18 ml/min, and underlying renal diseases were similar to registry data. Mean arterial pressure (MAP) achieved was 99.4+/-14.4 and 98.9+/-11.9 mmHg in individuals with >1 and </=1 g/day proteinuria, respectively. When similarly stratified by proteinuria, mean systolic blood pressures were 141.4+/-23.5 and 140.9+/-20.3 mmHg, and mean diastolic blood pressures were 78.4+/-14.0 and 77.9+/-11.4 mmHg, respectively. Blood pressure control, according to published guidelines, was achieved in 128 patients (42.1%). A further 86 (28.3%) patients had their AHM increased. The remaining 90 (29.6%) did not have their AHM increased. Of these, 40 were labelled 'at target blood pressure' (mean MAP 100.5+/-5.4 mmHg), 19 'office hypertension' and 11 'unfavourable risk/benefit ratios'. There were 108/304 (35.5%) patients who were not taking ACEI or ARB (angiotensin receptor antagonist): 34/108 (31%) had previous ACEI failure due to hyperkalaemia (21/108, 19%) or acute renal failure (17/108, 16%), and 61/108 (55%) were felt 'unlikely to benefit' (categories not mutually exclusive). Miscommunication with the primary physician and medication costs were not identified as significant barriers to improved blood pressure control or ACEI use. CONCLUSIONS: Approximately 40% of CRI patients are achieving current blood pressure goals and 64% are prescribed ACEI/ARB in tertiary care nephrology clinics. Although the use of these strategies may be increasing, there remains room for improvement. Physicians should remain aware of the need to use these proven strategies in patients with CRI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Access flow monitoring of patients with native vessel arteriovenous fistulae and previous angioplasty.

Screening strategies based on measurement of access blood flow (Qa) allow detection and angioplasty of subclinical stenosis in native vessel arteriovenous (AV) fistulae. However, little is known about the efficacy of Qa measurements for detecting recurrent stenoses in fistulae and that of angioplasty for correcting them. A total of 303 patients were studied over 30 mo; 69 (23%) of these had stenoses, of whom 53 underwent angioplasty. Of those undergoing angioplasty, 30 patients had 46 episodes of recurrent positive studies and underwent repeat fistulography. In 31 of these episodes (19 patients), stenosis was again identified and treated successfully with angioplasty. Overall positive predictive values for stenosis were similar in first and subsequent episodes of stenosis (71% versus 67%), and angioplasty was associated with sustained increases in Qa for both first and subsequent episodes. Assisted patency in fistulae that required repeat angioplasty was 87% (median follow-up 10 mo after the second angioplasty). In conclusion, Qa is effective for detecting first and subsequent lesions in patients with AV fistulae, and angioplasty of first or subsequent lesions is associated with sustained increments in Qa. Continued screening after correction of first stenoses appears reasonable, because of both the frequency of recurrent stenosis and the success of repeat intervention.

Angioplasty, Balloon↗
PubMed2001

Screening for subclinical stenosis in native vessel arteriovenous fistulae.

Guidelines recommend the use of ultrasound dilution techniques (UDT), including measurement of access recirculation (AR) and access blood flow (Q(a)), to screen for subclinical vascular access dysfunction. Although these techniques are efficacious in polytetrafluoroethylene grafts, data in native vessel arteriovenous fistulae (AVF) are lacking. A prospective observational study was conducted to evaluate the utility of UDT screening in AVF. Q(a) and AR were measured bimonthly. Positive studies required fistulograms and were defined by Q(a) < 500 ml/min, DeltaQ(a) > 20% from baseline or AR > 5%. Accesses with stenosis underwent percutaneous angioplasty. After 1 yr, there were 1355 mo of follow-up in 177 patients. There were 44 positive studies in 40 patients. Q(a) was <500 ml/min in 36 (82%), DeltaQ(a) was >20% in 5 (11%), and AR was >5% in 6 (14%). Of patients with Q(a) < 500 ml/min, 29 (81%) had stenosis. Only two patients (40%) with DeltaQ(a) > 20% but Q(a) > 500 ml/min had stenosis. No patient with AR > 5% had stenosis unless Q(a) was also <500 ml/min. Immediate patency rate was 93% post-PTA. Mean Q(a) increased from 303 +/- 154 ml/min to 602 +/- 220 ml/min (P < 0.0001), and mean urea reduction ratio increased from 70.4 +/- 8.4% to 74.6 +/- 6.5% (P = 0.003) post-PTA. The results demonstrate that UDT could detect subclinical stenoses in AVF, and most lesions were amenable to angioplasty. AVF that underwent PTA delivered higher Q(a) and urea reduction ratio, and immediate patency rates were acceptable. Access failure after negative UDT was unusual. Measuring AR increases the time required to perform UDT but does not improve utility. Serial measurements of Q(a) alone may be the best strategy for screening AVF.

Aged↗