[Show abstract][Hide abstract] ABSTRACT: In the 1993 two papers showed that instantaneous ionic dialysance can be measured without the need for blood or dialysate sampling and at no extra cost, simply by using two conductivity probes placed at the dialyzer inlet and outlet or a single probe alternately activated at the inlet and outlet. Given the very close correlation between the conductivity of dialysate and its sodium content it has been suggested that ionic dialysance can be considered equivalent to effective sodium dialysance. When ionic dialysance value is known it is possible to indirectly derive the plasma water conductivity value and thus the sodium concentration. The possibility to estimate sodium dialysance and plasma water sodium concentration without the need for blood samples and laboratory determination makes it very easy to apply the sodium kinetic model changing it in a conductivity kinetic model. Moreover, because of the similar molecular weight of sodium chloride and urea it has been suggested that ionic dialysance can also be considered equivalent to effective urea clearance. Thus, it should be possible to use ionic dialysance instead of urea clearance for the routine monitoring of delivered dialysis dose. Therefore, ionic dialysance seems a very promising and easy tool to improve dialytic treatment.
[Show abstract][Hide abstract] ABSTRACT: Anemia is a common complication of patients receiving peritoneal dialysis (PD) but has been little studied compared to other chronic kidney disease (CKD) populations. A number of factors can affect its severity or response to erythropoiesis-stimulating agents (ESA). Some, such as iron deficiency, occult blood loss, infection, inflammation, oxidative stress, inadequate dialysis dose, and hyperparathyroidism are common to all dialysis patients but they may be more or less important depending on dialysis modality. The net balance of their contribution explains the fact that on average PD patients require less ESA doses compared to hemodialysis patients to correct anemia and maintain stable Hb levels. As in other CKD patients, low hemoglobin levels have been associated with increased mortality in PD patients. Unfortunately, no clinical trials have been carried out specifically in this population whether aiming at different Hb targets with ESAs may modify patient outcome. Given the lack of a vascular access, it is advisable to give PD patients ESA therapy subcutaneously. Long-acting molecules may be of advantage, especially when the drug is administered at the dialysis center.
Contributions to nephrology 01/2012; 178:89-94. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Today, hemodialysis (HD) represents a rescue therapy for an increasing number of patients worldwide. Thanks to continuous improvements, it is now better tolerated; thus, allowing patients relief from uremic symptoms and increasing survival. However, many questions regarding the best way of ameliorating the outcomes of chronic kidney disease patients requiring dialysis are still open. Recently, 2 randomized controlled clinical trials tried to give some answers to the current debates around dialysis. The first one--the IDEAL trial--evaluated the effects of beginning early or late dialysis on patient mortality and morbidity, and it did not find any significant difference between the 2 groups, suggesting that starting dialysis on the basis of an estimate of GFR alone is not suitable. The second one--the FHN daily trial--compared in-center conventional (3 times per week) with in-center frequent (6 times per week) HD. It found that daily dialysis is associated with improvements in left ventricular mass, physical health composite scores and some secondary outcomes (hypertension and hyperphosphatemia) - although it also discovered there had been more frequent interventions related to vascular access. Despite the fact that both studies presented some unavoidable limitations, they gave important information which is useful in everyday clinical practice. According to evidence-based medicine, such well-designed and well-conducted randomized controlled trials are the best way to improve our knowledge.
Contributions to nephrology 01/2011; 171:30-8. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many observational studies have consistently shown that high-flux hemodialysis (hf-HD) has positive effects on the survival and morbidity of chronic kidney disease stage 5 dialysis (CKD5D) patients when compared with low-flux hemodialysis, but the primary analysis of the prospective randomized Hemodialysis Outcomes (HEMO) study showed that the use of hf-HD was not associated with a significant reduction of the relative risk of mortality. More recently, the Membrane Permeability Outcome (MPO) study found that survival could be significantly improved by use hf-HD compared with low-flux dialysis in high-risk patients as identified by serum albumin ≤4 g/dl and, in a post-hoc analysis, in diabetic patients. Online hemodiafiltration (HDF) is reported as the most efficient technique of using high-flux membranes. Clearances of small solutes like urea are higher than in hemofiltration and of middle solutes like β(2)-microglobulin are higher than in hf-HD. As the number of randomized prospective trials comparing HDF and hf-HD is still very limited, no conclusive data are available concerning the effect of increased convection of online HDF on survival and morbidity in CKD5D patients. A large, randomized controlled study is needed to clinically confirm the theoretical advantages of online HDF.
Contributions to nephrology 01/2011; 168:5-18. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Anemia secondary to chronic kidney disease is a complex syndrome. Adequate dialysis can contribute to its correction by removing small and possibly medium/large molecules that may inhibit erythropoiesis. A clear relationship among hemoglobin, erythropoiesis stimulating agent (ESA) dose and increase in dialysis dose has been pointed out by a number of prospective and retrospective studies. Increasing attention has also been paid to the relationship between dialysis, increased inflammatory stimulus and ESA response, as dialysate contamination and low compatible treatments may increase cytokine production and consequently inhibit erythropoiesis. As medium/large molecular weight inhibitors can be removed only by more permeable membranes, convective treatment sand, particularly, online treatments, could theoretically improve anemia correction by two mechanisms: higher removal of medium and large solutes (possibly containing bone marrow inhibitors) and reduced microbiological and pyrogenic contamination of the dialysate. Unfortunately, available results are conflicting. Large, prospective, randomized studies on this topic are still needed.
Contributions to nephrology 01/2011; 168:162-72. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The theoretical advantages of high-flux hemodialysis (HD) in treating patients with chronic kidney disease (CKD) stage 5 are related to the higher toxin removal (especially 'middle molecules'), including sodium and water, and to the better biocompatibility of the treatment, including membrane and water quality. Several observational studies have shown that high-flux HD has positive effects on the survival and morbidity of uremic patients when compared with low-flux HD. The primary analysis of the prospective randomized HEMO (Hemodialysis Outcomes) study showed that high-flux HD was associated with an 8% nonsignificant reduction of mortality in comparison with low-flux HD. However, a secondary analysis pointed to an advantage for high-flux HD in subgroups of patients. More recently, the MPO (Membrane Permeability Outcome) study found that survival could be significantly improved by using high-flux HD compared with low-flux HD in high-risk patients as identified by serum albumin ≤4 g/dl and, in a post hoc analysis, in diabetic patients as a whole. On-line hemodiafiltration (HDF) is considered the most efficient technique of using high-flux membranes. Clearance of small solutes like urea are higher than in hemofiltration, and clearance of middle solutes like β(2)-microglobulin are higher than in high-flux HD. Since there is only a very limited number of randomized prospective trials comparing HDF and high-flux HD, no conclusive data are available about the effect of increased convection of on-line HDF on survival and morbidity of CKD patients. The suggested advantages of HDF must be confirmed by a large randomized controlled study.
Contributions to nephrology 01/2011; 171:92-100. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many observational studies have consistently shown that high-flux hemodialysis has positive effects on the survival and morbidity of uremic patients when compared with low-flux hemodialysis. However, the HEMO study, a randomized trial designed to evaluate the effect of membrane permeability on patient survival, showed only an 8% non-statistically significant reduction of mortality, albeit a secondary analysis suggested an advantage for high-flux membranes in certain patient subgroups. The prospective, randomized Membrane Permeability Outcome (MPO) study investigated the impact of membrane permeability on survival in incident hemodialysis patients who had low albumin (≤4 g/dl) and normal albumin ( >4 g/dl) as separate randomization groups. Patients with serum albumin ≤4 g/dl had significantly better survival rates in the high-flux group compared with the low-flux group (p = 0.032). Moreover, a post-hoc secondary analysis showed that high-flux membranes may significantly improve survival in diabetic patients. No difference was found in patients with normal albumin levels. Considering the increasing number of dialysis patients with low serum albumin levels and with diabetes, the relevance of the MPO study led to the publication of a position statement by the European Renal Best Practice Advisory Board. This board strongly recommended that high-flux hemodialysis should be used for high-risk patients and, with a lower degree of evidence, even also for low-risk subjects due to the substantial reduction in β(2)-microglobulin levels observed in the high-flux group.
Contributions to nephrology 01/2011; 175:81-92. · 1.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Erythropoiesis stimulating agents (ESAs) are effective drugs that correct anemia in patients with chronic kidney disease (CKD). Recombinant human erythropoietin (EPO), the first ESA that became available more than 20 years ago, is similar to the naturally occurring molecule. In subsequent years, pharmacological research focused on the development of new agents with improved characteristics, with the creation of high molecular weight ESAs having been the first approach. In more recent years, new agents have been developed, including peginesatide (Hematide; Affymax Inc/Takeda Pharmaceutical Co Ltd), which is a dimeric peptide with a chemical structure unrelated to EPO that is being evaluated in phase III clinical trials. In addition, the clinical development of two inhibitors of hypoxia-inducible transcription factor has been resumed recently, while other approaches, such as gene therapy and EPO fusion proteins, and the inhibition of GATA and hematopoietic cell phosphatase remain far from being applicable in clinical practice. New iron compounds, which are becoming increasingly available, will facilitate an integrated approach to anemia management using both iron and/or ESAs, according to the clinical needs of patients. This review discusses new therapeutic options (already available or still under development) for the treatment of CKD-associated anemia, including ESAs and intravenous iron molecules.
Current opinion in investigational drugs (London, England: 2000) 09/2010; 11(9):1030-8. · 3.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hemodialysis was born in 1945 to treat acute renal failure, and it has progressively become a rescue therapy for patients with chronic kidney disease (CKD) stage 5, otherwise doomed to death. During the years, technological innovations have led to improved dialytic tolerance, making possible to extend the treatment to a greater number of subjects. Low- and high-flux bicarbonate dialysis are nowadays the most frequent hemodialysis techniques; hemodiafiltration with different modalities, short daily and overnight hemo-dialysis are also widespread, each of them with peculiar characteristics. A recent randomized controlled clinical trial has identified high-flux hemodialysis as the best treatment for patients with low serum levels of albumin and for diabetics in comparison to low flux dialysis. Apart from the treatment of end-stage renal disease (ESRD), hemodialysis has new and important applications, including heart failure treatment and multiple myeloma. The need to provide hemodialysis patients a better quality of life has increased the interest in developing new techniques, such as the wearable artificial kidney, although still in initial clinical development. During the last 60 years, we have seen an exciting evolution in the field of hemodialysis, which has led to important changes in the outcome of ESRD patients. The preclinical and clinical hard work ongoing in earlier stages of CKD should be able to obtain further relevant improvements and maybe avoid the need of hemodialysis itself.
Minerva urologica e nefrologica = The Italian journal of urology and nephrology 03/2010; 62(1):1-11. · 0.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although the prognosis of patients who have diabetes and are receiving renal replacement therapy has greatly improved, survival and medical rehabilitation rates continue to be significantly worse than those of nondiabetic patients, mainly because of pre-existing severely compromised cardiovascular conditions. In this scenario, the nephrology community had to do its best in order to offer the best treatment options to these patients using a multifaceted approach. The most common RRT modality in patients with diabetes is still hemodialysis, but it gives rise to a number of clinical problems, in particular difficulties in the management of the vascular access and high frequency of intradialytic hypotension. Recent data suggest that efficient high-flux treatments have the potential of improving morbidity and mortality of diabetics with ESRD. Sodium profiling during the dialysis session may be also of importance in reducing intradialytic hypotension and helping in achieving the prescribed body weight. Patients who have diabetes and are on peritoneal dialysis have to face a progressive increase in peritoneal permeability, loss of ultrafiltration, and peritoneal fibrosis, all phenomena being accelerated in patients with diabetes and ultimately leading to an increased technique failure. However, the two dialytic modalities are comparable in terms of outcomes in the short term.
Seminars in Dialysis 02/2010; 23(2):214-9. · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The great increase in the number of patients with chronic kidney disease (CKD) can be explained by a number of reasons. Elderly patients present typical and peculiar clinical features, and nephrologists have to consider the frequent clinical complications related to old age, such as malnutrition and cachexia, cognitive impairment and physical dependence with walking disability and depression. All of these factors have led to the birth of geriatric nephrology. Geriatric nephrology needs to take into account the high prevalence of diabetes and vascular disease in the elderly, which is related to a poor prognosis, mainly related to cerebrocardiovascular mortality. Best everyday clinical practice should include an accurate evaluation of patients, including quality of life, to select the best therapeutic approach for each individual case. A careful and reasonable use of drugs in the elderly is also of importance.
[Show abstract][Hide abstract] ABSTRACT: Intradialytic hypertension is not a rare complication of dialysis, with a prevalence of 5-15% among hemodialysis patients, and it seems to be associated with adverse outcomes. This complex phenomenon is not well understood, and many uncertainties exist regarding its pathophysiologic mechanisms and appropriate treatment strategies. Mechanisms that might be involved in the pathogenesis of intradialytic hypertension include extracellular volume overload, increased cardiac output, changes in electrolyte levels (particularly sodium), activation of the renin-angiotensin-aldosterone system, overactivity of the sympathetic nervous system, and endothelial cell dysfunction. Most current treatment strategies are based only on expert opinion and not on the results of randomized clinical trials, as very little data on the therapy of intradialytic hypertension are available. The most important treatment is adequate sodium and water removal, but reducing sympathetic hyperactivity and reducing endothelin-1 levels should also be considered. Well-designed, randomized clinical trials are urgently needed to better understand the pathophysiologic mechanisms of this complex phenomenon and to improve its diagnosis, prognosis and treatment.
[Show abstract][Hide abstract] ABSTRACT: The clinical benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) are well established in chronic kidney disease (CKD) patients with diabetic and non-diabetic nephropathies. But despite appearance, the magnitude of this effect has been questioned particularly in mild, proteinuric nephropathies. Given that the single agents can achieve only partial and not durable suppression of the renin-angiotensin system (RAS), it has been hypothesized that dual blockage with ACE inhibitors and ARBs would be most beneficial in the management of progressive CKD than either agent alone. Available evidence indicates significant anti-proteinuric effect, but long-term data in CKD patients are lacking. Recently, the findings of the ONTARGET trial even questioned the safety of this therapeutic approach. Given that preventing cardiovascular complications is extremely important in CKD and RAS inhibition may be useful in this setting, benefits of RAS blockade must be weighed against its possible adverse effects particularly in elderly patients.
Nephron Clinical Practice 10/2009; 113(4):c286-93. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Convective treatments are characterized by enhanced removal of middle and large molecular weight solutes, important in the genesis of many complications of hemodialysis, compared with conventional low-flux hemodialysis. The availability of these techniques represented an intriguing innovation and a possible means to improve the still poor prognosis of hemodialysis patients. In this study we will critically review the most important published studies evaluating the impact of convective treatments on dialysis outcomes.
The Hemodialysis (HEMO) study showed that greater urea removal nonsignificantly reduces the relative risk of mortality and that also high-flux hemodialysis was associated with a nonsignificant reduction, although a secondary analysis pointed to an advantage for high-flux membranes in subgroups of patients. More recently, the Membrane Permeability Outcome (MPO) study found that survival could be improved by use of high-flux membranes compared with low-flux dialysis in high-risk patients as identified by serum albumin < or =4 g/dl as well as in people with diabetes. In an observational study, hemodiafiltration with large reinfusion volume has been associated with a lower relative risk of mortality, compared with low-flux hemodialysis.
The biologic plausibility of advantages of convective treatments and the results of the MPO and Dialysis Outcomes and Practice Patterns (DOPPS) studies are supporting rationales for the use of convective treatments to improve survival and delay long-term complications of hemodialysis patients.
Current opinion in nephrology and hypertension 09/2009; 18(6):476-80. · 3.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients on peritoneal dialysis (PD) with high small solute peritoneal membrane transport have an increased risk of morbidity and mortality. The membrane transport is currently assessed by peritoneal equilibration test (PET), usually performed after the first month of PD because of the early increase of membrane transport after the start of PD. The aim of this study was the assessment of small solute peritoneal membrane transport before and after the start of PD.
The small solute peritoneal membrane transport was evaluated in 34 patients before the start of PD. Twenty-two patients were treated with continuous ambulatory peritoneal dialysis (CAPD) and 12 with automated peritoneal dialysis (APD).
Four months after the start of PD, the small solute peritoneal membrane transport increased only in CAPD patients (D/P(Creat), the ratio between dialysate solute concentration at the end of the PET and creatinine plasma concentration, changed from 0.66 +/- 0.12 to 0.73 +/- 0.07 in CAPD patients and from 0.64 +/- 0.12 to 0.61 +/- 0.07 in APD patients), and after about 16 months of PD, the peritoneal membrane transport was higher in CAPD patients (D/P(Creat) = 0.74 +/- 0.06) than in APD patients (D/P(Creat) = 0.63 +/- 0.10).
Performing the PET before and after the start of PD could provide relevant information about the characteristics of small solute peritoneal membrane transport and could be useful to evaluate the influence of PD modality on the changes in peritoneal membrane transport.
[Show abstract][Hide abstract] ABSTRACT: Therapy with erythropoiesis-stimulating agents (ESAs) is a well-established treatment for renal anemia. ESAs are highly effective at correcting the underlying anemia, restoring energy levels and increasing patient well-being and quality of life. Anemia correction has considerable secondary benefits in terms of morbidity and mortality reduction. However, because of the relatively short halflife of ESAs, they generally have to be administered one to three times weekly in most patients. In order to overcome this shortcoming, in recent years pharmacological research has tried to modify the molecular structure of recombinant human erythropoietin (rHuEpo) in order to improve pharmacokinetics and pharmacodynamics and to allow a reduction in the frequency of administration. Covalent addition of the water-soluble polyethylene glycol moiety has been successfully used to improve the pharmacokinetics of a number of proteins and reduce their immunogenicity. A modified version of rHuEPO incorporating this large polymer chain, called continuous erythropoiesis receptor activator (CERA), has been recently synthesized. Data from animal studies indicate that CERA has a prolonged half-life in comparison with rHuEPO that may allow less frequent administration. Results of phase II and III clinical trials suggest that this agent is effective in maintaining hemoglobin levels after switching from rHuEPO therapy or darbepoetin alpha when administered up to once a month. This less frequent administration schedule may be an advantage for patients and healthcare providers. In addition, this agent may give increased hemoglobin stability over time.
[Show abstract][Hide abstract] ABSTRACT: Standard hemodialysis is a far from ideal treatment for uremia since the morbidity and mortality of patients on hemodialysis are still significantly higher than those of non-hemodialyzed subjects with similar demographic characteristics. Because it has been suggested that the cause could lie in the inadequate removal of ''middle molecules'' by standard hemodialyis, two alternative treatments have been proposed: high-efficiency hemodialyis and high-flux hemodialyis. The 2002 results of the HEMO study showed that both these treatments are associated with a non-significant reduction in the relative risk of death (4% and 8%, respectively). The MPO study, which - unlike the HEMO study - enrolled only incident cases and not did not allow reuse of dialyzers, evaluated the mortality rate with high-flux and low-flux hemodialysis in a sicker population, i.e., patients with hypoalbuminemia, and showed a significant reduction in the relative risk of death especially in patients with diabetes. In an attempt to define the clinical impact of hemodiafiltration, some of the efficacy data from clinical studies are reviewed in light of a number of factors that may be related to the high mortality among hemodialysis patients. The current state of affairs suggests it is reasonable to prefer high-flux hemodialysis in sicker patients, especially diabetics. Moreover, the use of ultrapure dialysis fluid is recommended to reduce chronic inflammation and its consequences.
Giornale italiano di nefrologia: organo ufficiale della Societa italiana di nefrologia 26 Suppl 45:S16-9.