Search

Background: Patients with chronic renal failure commonly suffer from a secondary form of complex dyslipidaemia, and may benefit from lipid-lowering treatment. Atorvastatin has been shown to reduce efficiently the levels of atherogenic lipoproteins also in patients with renal failure, but pharmacokinetic data in haemodialysis patients are lacking., Methods: In this study, hypercholesterolaemic haemodialysis patients received 40 mg (n=12) or 80 mg (n=11) atorvastatin once daily, first as a single dose and then continuously for 2 weeks. Plasma levels of atorvastatin and its active and inactive metabolites were measured by LC/MS/MS, and pharmacokinetic parameters (C(max), t(max), AUC, t(1/2)) compared between single and multiple dosing, and between the different doses., Results: The pharmacokinetic parameters of the parent drug atorvastatin acid were not significantly different after single and 2-week multiple dosing; they showed dose-proportionality between the 40 and 80 mg dose, and were comparable to findings in healthy volunteers. Dose-proportionality and absence of accumulation was also observed for the major active metabolite ortho-hydroxy-atorvastatin and the inactive metabolites atorvastatin lactone and ortho-hydroxy-atorvastatin lactone, but the levels of the active metabolite were relatively lower, and the inactive metabolites higher, compared with healthy volunteers. The para-hydroxy-metabolites constituted only a minor pathway in atorvastatin's metabolic elimination. Haemodialysis did not cause enhanced clearance of atorvastatin or its metabolites, the drug was well tolerated and there were no serious adverse events., Conclusion: While subtle differences may exist in the metabolic processing of atorvastatin in haemodialysis patients, active drug did not accumulate nor did it show enhanced elimination, and levels were comparable to those measured in healthy volunteers. Therefore there is no need to adapt atorvastatin dosage in this particular patient population.

Background: In healthcare economics, the cost factor plays a leading role, particularly for chronic diseases such as end-stage renal disease because of the growing number of patients., Objectives: An international comparison was made of the costs and reimbursement/funding of a selection of key dialysis modalities--centre haemodialysis (CHD), limited care haemodialysis (LCHD), home haemodialysis (home HD), continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD)--in various industrial countries. The focus was on treatment costs plus erythropoietin medication and reimbursement of transportation costs., Results: Reimbursement/funding of dialysis is different from country to country, with some healthcare system-specific commonalities: in 'public' systems, the funding is based more on global budgets, whereas in mixed public and private countries it is based mainly on reimbursement rates per treatment. Only in the 'private system' of the US is there one DRG (diagnostic-related group)-type rate for dialysis. By comparing the costs (in public countries) or reimbursements (in mixed countries) of treatment modalities within each country, we could see similar curves: the costs were the highest for public CHD, followed by private CHD. They were lower on LCHD and the lowest for home HD and CAPD, which were at nearly the same level. The cost level for APD was almost the same as that of LCHD. The reimbursements followed the cost pattern. Some countries introduced increases for CAPD and APD with the intention of increasing the share of home care. The costs and reimbursement patterns in the majority of countries (except the US and Japan) were very similar and therefore did not explain the different distribution of modalities in these countries. One explanation could be, however, the difference in microeconomics, CHD being a treatment with high fixed costs (personnel and structure) and CAPD being a treatment with low fixed costs, but high variable costs (supplies) and a low need for investments., Discussion: The choice of treatment modality seems to be influenced strongly by the provider's perspective, being either public with limited HD capacity or private having invested in HD capacity. For public providers (and healthcare payers), CAPD is less expensive than CHD and offers a number of potential savings. In many countries, two CAPD patients could be treated for the same costs as one CHD patient. The microeconomics of private centres, however, are meant to use the investments maximally for CHD. Only if capacity limits are reached, is PD, with mainly supply costs, interesting. The future with constantly increasing numbers of patients and growing cost constraints will force all providers to make the best use of their resources by also offering home therapies such as PD to patients. The latter are cost efficient and offer comparable survival and quality of life.

In end-stage renal disease (ESRD), the human recombinant erythropoietin doses required to keep haemoglobin in the target range may vary considerably between patients. Previous studies have failed to find any predictive factor of the response. We thus performed the present investigation in 30 ESRD patients to discover if the haematological response to human recombinant erythropoietin (rHuEpo) was related to the results of circulating erythroid progenitor cultures. Peripheral erythroid burst forming units (BFU-E) were cultured in a plasma clot system in the absence or in the presence of autologous serum just before starting rHuEpo therapy. The results showed a higher BFU-E number in ESRD patients than in controls and a stimulatory effect of autologous serum in both patients and controls. Comparison between culture results and haematological response yielded positive correlation between the BFU-E number and the haemoglobin increase during the first month of treatment, and negative correlation between the increase of BFU-E numbers during the first week of therapy and the rHuEpo doses required for a long-term response. We thus conclude that in ESRD patients the individual response to rHuEpo is linked to the numbers of circulating BFU-E.

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.

We compared plasma beta-2-microglobulin (beta 2M) at a 1-year interval in 25 CAPD patients and 25 patients haemodialysed with cuprophane membranes and matched for residual renal function and duration of renal replacement therapy. Plasma beta 2M remained lower in CAPD patients throughout the study, and increased significantly with time both in CAPD and haemodialysis patients, as renal function decreased. In both groups, plasma beta 2M was negatively correlated with residual creatinine clearance, the influence of the latter being much greater in haemodialysis, as demonstrated by comparison of the regression lines. In haemodialysis, but not in CAPD, plasma beta 2M also correlated with time on dialysis. In CAPD patients, the daily peritoneal output averaged 38 mg (range 16-59 mg), and was directly correlated with plasma beta 2M. CAPD thus allows a significant peritoneal removal of beta 2M, which progressively takes over from the declining renal function, resulting in lower plasma beta 2M than in matched haemodialysis patients. However, the peritoneal removal of beta 2M remains insufficient and values increase with time as renal function declines. Thus, if beta 2M amyloidosis is related to raised plasma levels, the risk of beta 2M amyloidosis in CAPD should simply be delayed as compared to haemodialysis.