Bart Maes

Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test

BACKGROUND The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing. METHODS A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase. RESULTS There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test. CONCLUSIONS It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.

Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial

BACKGROUND Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. METHODS We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. FINDINGS After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. INTERPRETATION Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

Long‐term Cardiac Outcomes in Renal Transplant Recipients Receiving Fluvastatin: The ALERT Extension Study

Renal transplant recipients (RTR) have an increased risk of premature cardiovascular disease. The ALERT study is the first trial to evaluate the effect of statin therapy on cardiac outcomes following renal transplantation. Patients initially randomized to fluvastatin or placebo in the 5–6 year ALERT study were offered open‐label fluvastatin XL 80 mg/day in a 2‐year extension to the original study. The primary endpoint was time to first major adverse cardiac event (MACE). Of 1787 patients who completed ALERT, 1652 (92%) were followed in the extension. Mean total follow‐up was 6.7 years. Mean LDL‐cholesterol was 98 mg/dL (2.5 mmol/L) at last follow‐up compared to a pre‐study level of 159 mg/dL (4.1 mmol/L). Patients randomized to fluvastatin had a reduced risk of MACE (hazards ratio [HR] 0.79, 95% CI 0.63–0.99, p = 0.036), and a 29% reduction in cardiac death or definite non‐fatal MI (HR 0.71, 95% CI 0.55–0.93, p = 0.014). Total mortality and graft loss did not differ significantly between groups. Fluvastatin produces a safe and effective reduction in LDL‐cholesterol associated with reduced risk of MACE in RTR. The lipid‐lowering and cardiovascular benefits of fluvastatin are comparable to those of statins in other patient groups, and support use of fluvastatin in RTR.

Influence of dietary protein supplements on the formation of bacterial metabolites in the colon.

BACKGROUND: To evaluate the influence of increased dietary protein intake on bacterial colonic metabolism in healthy volunteers. METHODS: Short chain fatty acids, ammonia, and volatile organic compounds in faecal samples, and phenols in the urine of five volunteers were measured after one week of basal nutrient intake and and after one week of a diet supplemented with a protein rich food (Fortimel; Nutricia, Zoetermeer, The Netherlands). Paired t tests and factor analysis were used for statistical analysis. RESULTS: Total energy and resistant carbohydrate intake remained unchanged in each study period. The percentage energy intake delivered as dietary protein, increased significantly (from 15.4% to 23.8%; p = 0.007) during supplement intake. A significant increase in faecal ammonia (p = 0.002), faecal valeric acid (p = 0.02), and urinary p-cresol (p = 0.04) was noted during supplementary protein intake. A total of 120 different volatile compounds were isolated from the faecal samples of which 10 increased significantly during dietary protein supplementation. The change in volatile pattern, especially for S containing metabolites, was clearly shown by a factor analysis model which made a distinction between the two dietary regimens for all volunteers. CONCLUSION: An increase in dietary protein leads to altered products formation by colonic metabolism, mainly reflected by an increase in faecal ammonia, faecal volatile S substances, and urinary p-cresol.

Prospective Study on Late Consequences of Subclinical Non-Compliance with Immunosuppressive Therapy in Renal Transplant Patients

In this prospective study we compared the incidence of late acute rejections (LAR) and changes in serum‐creatinine over time between compliers and noncompliers with immunosuppressive therapy more than 1 year post transplantation and explored the relative contribution of non‐compliance and other risk factors in the occurrence of LAR.

Efficacy, Tolerability, and Safety of Lanthanum Carbonate in Hyperphosphatemia: A 6-Month, Randomized, Comparative Trial versus Calcium Carbonate

Background/Aims: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. Methods: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. Results: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. Conclusion: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750–3,000 mg/day) is similar to that seen with calcium carbonate (1,500–9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.

Clinical efficacy and toxicity profile of tacrolimus and mycophenolic acid in relation to combined long-term pharmacokinetics in de novo renal allograft recipients.

Tacrolimus and mycophenolate mofetil are effective drugs characterized by specific toxicity profiles that may compromise their long‐term use in renal transplant recipients. Clinicians, therefore, need reliable drug monitoring tools for relating efficacy and toxicity to drug exposure.

Posttransplantation diabetes mellitus in FK-506-treated renal transplant recipients: analysis of incidence and risk factors

BACKGROUND The development of posttransplantation diabetes mellitus has a major impact on the quality of life and long-term outcome. METHODS One hundred thirty-nine patients without known glucose metabolism abnormalities and treated with FK-506, methylprednisolone, and mycophenolate mofetil/azathioprine were analyzed for incidence of and risk factors for developing impaired fasting glycemia (IFG) and diabetes mellitus (DM). RESULTS Using the American Diabetes Association criteria, 15% developed IFG and 32% developed DM in the first year after transplantation. High trough levels of FK-506 during the first month after transplantation (especially >15 ng/ml) and high body mass index (BMI) were significant risk factors for IFG or DM. Patients with (steroid-treated) acute rejections in addition to high trough levels of FK-506 were most prone to develop DM, whereas high BMI conferred risk of developing IFG. Patients with posttransplantation glycemic abnormalities also had higher levels of serum triglycerides at the time of transplantation, but they needed a lower dose of FK-506 to obtain higher trough levels of FK-506, suggesting metabolic differences already present before transplantation. The only risk factor retained for persistent IFG or DM beyond the first year was a higher number of trough levels of FK-506 >15 ng/ml during the first month after transplantation. CONCLUSIONS Induction with an FK-506 based immunosuppressive regimen resulted in a high incidence of glucose metabolism disorders in renal transplantation recipients. Higher trough levels of FK-506 during the first month, acute rejections, and higher BMI were the most obvious risk factors.

Risk factors for cardiovascular events after successful renal transplantation

Background. Cardiovascular disease is a frequent cause of morbidity after renal transplantation. The aims of this study were to evaluate the incidence of cardiovascular events and to identify the main risk factors for cardiovascular complications and mortality in 2071 white adults with a renal transplant functioning for at least 1 year. Methods. Clinical events, routine biochemistry, and prescribed drugs at month 1, month 6, and yearly after transplantation were analyzed. Results. The incidence of cardiovascular events increased over time. At 15 years after transplantation, only 47% of surviving patients had not experienced any cardiovascular event. Risk factors associated with cardiovascular complications were male gender (P=0.04), age (P<0.0001), arterial hypertension before transplantation (P<0.0001), longer pretransplant dialysis (P<0.0001), cardiovascular event before transplantation (P<0.0001), older era of transplantation (P=0.0009), center-specific effect (P=0.003), posttransplant diabetes mellitus (P=0.01), increased pulse pressure after transplantation (P=0.02), intake of corticosteroids (P=0.016), intake of azathioprine (P=0.016), lower serum albumin after transplantation (P=0.004), and higher serum triglyceride levels after transplantation (P=0.007). The risk of death was increased in patients with low or elevated hematocrit, while it was minimal with values around 38%. Conclusions. The occurrence of fatal and nonfatal cardiovascular events after successful renal transplantation not only relates to baseline cardiovascular risk factors present at transplantation, but also to immunosuppressive drugs and posttransplantation traditional and nontraditional risk factors.

Influenza vaccination is efficacious and safe in renal transplant recipients.

Whether influenza vaccination in solid‐organ transplant recipients is efficacious remains a controversial issue. Furthermore, theoretical concerns have been raised regarding the safety of vaccination as it might trigger rejection of the allograft. The present prospective trial is aimed at investigating the antibody response and safety of influenza vaccination in renal transplant recipients (RTR).