Showing papers in "Seminars in Dialysis in 2006"

Platelet dysfunction and end-stage renal disease.

Abstract: Patients with end-stage renal disease (ESRD) develop hemostatic disorders mainly in the form of bleeding diatheses Hemorrhage can occur at cutaneous, mucosal, or serosal sites Retroperitoneal or intracranial hemorrhages also occur Platelet dysfunction is the main factor responsible for hemorrhagic tendencies in advanced kidney disease Anemia, dialysis, the accumulation of medications due to poor clearance, and anticoagulation used during dialysis have some role in causing impaired hemostasis in ESRD patients Platelet dysfunction occurs both as a result of intrinsic platelet abnormalities and impaired platelet-vessel wall interaction The normal platelet response to vessel wall injury with platelet activation, recruitment, adhesion, and aggregation is defective in advanced renal failure Dialysis may partially correct these defects, but cannot totally eliminate them The hemodialysis process itself may in fact contribute to bleeding Hemodialysis is also associated with thrombosis as a result of chronic platelet activation due to contact with artificial surfaces during dialysis Desmopressin acetate and conjugated estrogen are treatment modalities that can be used for uremic bleeding Achieving a hematocrit of 30% improves bleeding time in ESRD patients

Neutrophil dysfunction and infection risk in end-stage renal disease.

Abstract: Infections are still a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients. The susceptibility of ESRD patients to infections is typically ascribed to the immunodeficient state associated with uremia. A central role in the host defense against bacterial infections is played by phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest and subsequently destroy bacteria. Disorders in polymorphonuclear cell function are exacerbated by the dialysis procedure and numerous factors including uremic toxins, iron overload, anemia of renal disease, and dialyzer bioincompatibility. It is concluded that the phagocytic defect observed in ESRD is multifactorial, and each factor should be managed individually with specific therapeutic approaches.

Leptin and renal disease.

Abstract: Leptin is a mediator of metabolism and disease in a variety of organ systems, most notably as an agent of energy stores. However, its role in renal disease as an inflammatory agent as well as its potential impact on the cachexia of uremia have sparked new interest in the molecule for nephrologists. This review elucidates the complex uremic state, the historical discovery of leptin and its physiology, and the potential interactions leptin has on both the progression of kidney disease as well as the morbidity and mortality of end-stage renal disease.

Pulmonary Hypertension in Hemodialysis Patients: An Unrecognized Threat

Abstract: Pulmonary hypertension (PH) is a progressive, fatal pulmonary circulatory disease that accompanies many conditions (including left to right side shunt) with compensatory elevated cardiac output. PH also complicates chronic hemodialysis (HD) therapy immediately after the creation of an arteriovenous (AV) access, even before starting HD therapy. It tends to regress after temporary AV access closure and after successful kidney transplantation. Affected patients have significantly higher cardiac output. This syndrome is associated with a statistically significant survival disadvantage. The laboratory hallmark of this syndrome is reduced basal and stimulatory nitric oxide (NO) levels. It appears that patients with end-stage renal disease (ESRD) acquire endothelial dysfunction that reduces the ability of their pulmonary vessels to accommodate the AV access-mediated elevated cardiac output, exacerbating the PH. Doppler echocardiographic screening of ESRD patients scheduled for HD therapy for the occurrence of PH is indicated. Early diagnosis enables timely intervention, currently limited to changing dialysis modality or referring for kidney transplantation.

The cardiovascular effects of arteriovenous fistulas in chronic kidney disease: a cause for concern?

Abstract: Arteriovenous fistulas (AVFs) are the preferred type of vascular access, but relatively little is known regarding their effects on cardiovascular remodeling and cardiac function. The following is a review regarding the immediate and long-term complications associated with AVF creation, including the development of left ventricular hypertrophy, high-output cardiac failure, exacerbation of coronary ischemia, and the possible contribution to the development of central vein stenosis.

Diagnosis and management of insomnia in dialysis patients.

Abstract: Sleep-related complaints affect 50-80% of patients on dialysis. Sleep disorders impair quality of life significantly. Increasing evidence suggests that sleep disruption has a profound impact both on an individual and on a societal level. The etiology of sleep disorders is often multifactorial: biologic, social, and psychological factors play a role. This is especially true for insomnia, which is the most common sleep disorder in different populations, including patients on dialysis. Biochemical and metabolic changes, lifestyle factors, depression, anxiety, and other underlying sleep disorders can all have an effect on the development and persistence of sleep disruption, leading to chronic insomnia. Insomnia is defined as difficulty initiating or maintaining sleep, or having nonrestorative sleep. It is also associated with daytime consequences, such as sleepiness and fatigue, and impaired daytime functioning. In most cases, the diagnosis of insomnia is based on the patient's history, but in some patients objective assessment of sleep pattern may be necessary. Optimally the treatment of insomnia involves the combination of both pharmacologic and nonpharmacologic approaches. In some cases acute insomnia resolves spontaneously, but if left untreated, it may lead to chronic sleep problems. The treatment of chronic insomnia is often challenging. There are only a few studies specifically addressing the management of this sleep disorder in patients with chronic renal disease. Considering the polypharmacy and altered metabolism in this patient population, treatment trials are clearly needed. This article reviews the diagnosis of sleep disorders with a focus on insomnia in patients on dialysis.

Lanthanum: a safe phosphate binder.

Abstract: Accumulation of inorganic phosphate due to renal functional impairment contributes to the increased cardiovascular mortality observed in dialysis patients. Phosphate plays a causative role in the development of vascular calcification in renal failure; treatment with calcium-based phosphate binders and vitamin D can further increase the Ca x PO(4) product and add to the risk of ectopic mineralization. The new generation of calcium-free phosphate binders, sevelamer and lanthanum, can control hyperphosphatemia without adding to the patients calcium load. In this article, the metabolism of lanthanum carbonate and its effects in bone, liver and brain are discussed. Although lanthanum is a metal cation its effects are not comparable to those of aluminum. Indeed, in clinical studies no toxic effects of lanthanum have been reported after up to four years of follow-up. The bioavailability of lanthanum is extremely low. The effects observed in bone are due to phosphate depletion, with no signs of direct bone toxicity yet observed in rats or humans. The liver is the main route of excretion for lanthanum carbonate, which can be localized in the lysosomes of hepatocytes. No lanthanum could be detected in brain tissue.

Electrolyte disturbances in the intensive care unit.

Abstract: The development of many electrolyte disturbances in the ICU can be prevented by attention to the use of intravenous fluids and nutrition Hyponatremia is a relative contraindication to the use of hypotonic intravenous fluids and hypernatremia calls for the administration of water Formulae have been devised to guide the therapy of severe hyponatremia and hypernatremia All formulae regard the patient as a closed system, and none takes into account ongoing fluid losses that are highly variable between patients Thus, therapy of severe hyponatremia and hypernatremia must be closely monitored with serial electrolyte measurements The significance of hypocalcemia in the critically ill is controversial Hypokalemia, hypophosphatemia, and hypomagnesemia should be corrected

Severe lactic acidosis treated with prolonged hemodialysis: recovery after massive overdoses of metformin.

Abstract: We report two cases of severe lactic acidosis due to massive metformin ingestion. The first case was a 37-year-old man who was discovered several hours after ingesting 45 g of metformin. He had severe lactic acidosis (blood pH 6.81, bicarbonate 4 mEq/L, lactate 25.7 mEq/L). Despite intravenous bicarbonate therapy, he decompensated and was placed on a combination of hemodialysis and charcoal hemoperfusion for a continuous time of 25 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has since made a complete recovery. The second case was a 53-year-old man who ingested 50 g of metformin. He also presented with severe lactic acidosis (blood pH 6.85, bicarbonate 3 mEq/L and lactate 28.4 mEq/L) and deteriorated despite intravenous bicarbonate therapy. He was placed on hemodialysis as a continuous therapy for 21 hours. His hospital course was complicated by acute renal failure requiring a period of intermittent hemodialysis. He has subsequently made a complete recovery. Metformin-associated lactic acidosis carries a high mortality rate. Prolonged hemodialysis should be considered as an early treatment option in these cases.

Dialysis-related amyloidosis: late finding or hidden epidemic?

Abstract: Dialysis-related amyloidosis is a complication of end-stage renal disease (ESRD) that results from retention of beta2-microglobulin (beta2M) and its deposition as amyloid fibrils into osteoarticular tissue. The clinical manifestations usually develop after several years of dialysis dependence and include carpal tunnel syndrome, destructive arthropathy, and bone cysts and fractures. High-flux membranes, daily dialysis, and hemofiltration all would be expected to delay the onset of dialysis-related amyloidosis because, to varying degrees, each increases the clearance of beta2M from the plasma. Thus what is currently a late complication of ESRD might become an even later complication as dialysis practices change. The significance of histologically evident but clinically silent beta2M amyloid, detectable not only in osteoarticular tissue but also in blood vessels, is unclear. Accumulating evidence that amyloidogenic proteins have direct and specific effects on cell processes irrespective of the extent of amyloid deposition raises the possibility that early, clinically silent beta2M amyloid deposits have unrecognized importance.

The Role of Continuous Renal Replacement Therapy in the Treatment of Poisoning

Abstract: Extracorporeal elimination of drugs and toxins is a critical component in the management of poisonings, though specific techniques and indications remain a matter of debate. Conventional hemodialysis is frequently the treatment of choice because of its widespread availability and proven effectiveness for certain drugs and toxins. With the increased availability of continuous renal replacement therapy (CRRT) modalities, there is yet another therapeutic option, but one that has yet to find a definitive role in this field. The continuous nature of these therapies is attractive for the management of acute renal failure, but the relatively slower clearance rates as compared to conventional hemodialysis is a distinct drawback in patients with acute xenobiotic-induced toxicity. There are abundant case reports as well as a few small case series in the medical literature documenting the use of CRRT, but specific techniques and the clinical outcomes vary considerably. Therefore one cannot draw definitive conclusions regarding benefit. Some patients, particularly those who are hemodynamically unstable and are not candidates for conventional hemodialysis, may warrant a trial of CRRT. However, at the present time, routine use for the treatment of poisoning is not supported. Controlled trials to better clarify its role would be beneficial, though such studies would be extremely difficult to conduct in this field. We believe that the intelligent application of extracorporeal modalities requires a thorough knowledge of drug pharmacokinetics, of the techniques utilized, and a skeptical analysis of the available literature.

Vascular Access Outcomes and Medication Use: A USRDS Study

Abstract: Several medications have been proposed to improve hemodialysis (HD) vascular access outcomes based on potentially favorable anticoagulant, antiplatelet, or pleiotropic properties. The purpose of this study was to evaluate the relationship between medication use and vascular access patency in a group of HD patients. We conducted a historical cohort study of the US Renal Data System Dialysis Mortality and Morbidity Wave II study to identify patients with an arteriovenous fistula (AVF), polytetrafluoroethylene (PTFE) graft, or a permanent catheter for vascular access. Cox regression analysis, adjusted for age, gender, race, history of coronary artery disease, peripheral vascular disease, or coronary artery bypass graft, was used to model the hazard ratio (HR) of permanent vascular access failure. Of the 2001 HD patients in the Wave II study, 901 (45%) were included in the analysis. PTFE graft patency was greater for males (HR, 0.73; 95% CI 0.53-1.00, p = 0.05) and for older individuals (HR, 0.99; 95% CI 0.98-1.00, p = 0.02). Treatment with antiplatelet medications, ticlopidine and dipyridamole (HR, 3.54; 95% CI 1.07-11.76; p = 0.04), or aspirin (HR, 2.49; 95% CI 1.31-4.73; p = 0.005) was associated with significantly worse AVF patency. Antiplatelet agents had a significant negative association with access patency in this cohort. In contrast to other published data, it was difficult to identify any beneficial effect of specific medications on access patency.

Long-term management of the tunneled venous catheter

Abstract: Despite their propensity for significant complications, tunneled central venous catheters have become a common means of vascular access in the United States for patients requiring maintenance hemodialysis for end-stage renal disease (ESRD). Reasons for their use include advanced patient age, peripheral vascular disease (arterial and venous), late referral for creation of vascular access, and more importantly, the lack of an interdisciplinary service line on vascular access among vascular surgeons, radiologists, and nephrologists. This review article summarizes complications commonly encountered in dialysis patients who use tunneled central venous catheters for vascular access-mainly thrombosis, stenosis, and infection. Special attention is given to novel approaches for the prevention of catheter-associated infections. Effective prevention and timely treatment of common catheter-associated complications can reduce the substantial morbidity associated with the use of these devices. However, these measures should not detract from the goal of avoiding or limiting the long-term use of catheters, thereby optimizing vascular access management by ensuring the timely availability of functioning arteriovenous fistulas.

Editorials: Nephrogenic Systemic Fibrosis: An Emerging Threat Among Renal Patients

Abstract: Nephrogenic systemic fibrosis (NSF), also known as nephrogenic fibrosing dermopathy, is a scleroderma-like disease of the skin observed in patients with renal insufficiency. Since its recognition in 1997, relatively little has been published in the nephrology literature, despite indications that the disorder is becoming increasingly recognized in the United States and abroad. As nephrology professionals may be the first to encounter newly developing cases of NSF, it becomes imperative that they be able to recognize the symptoms and comorbidities and initiate tests and treatment. To date, the cause of NSF has not been established. Recent observations indicate that specific cells normally involved in wound repair and tissue remodeling may be aberrantly recruited to the skin and soft tissues of NSF patients.

Lipid abnormalities associated with end-stage renal disease.

Abstract: Patients undergoing chronic renal replacement therapy have a high incidence of dyslipidemia. In general, there are increased concentrations of triglyceride-rich apolipoprotein B-containing particles. These elevations lead to increased levels of non-high-density lipoprotein (HDL) levels. This pattern is further modified by the method of dialysis (peritoneal versus hemodialysis) and comorbidities such as diabetes. End-stage renal disease patients also demonstrate increased levels of lipoprotein(a) (Lp(a)) and oxidized low-density lipoprotein (LDL)both of which are highly atherogenic. This review focuses on the pathogenesis of these lipid abnormalities and their role in the atherosclerotic process.

Complex bypasses and fistulas for difficult hemodialysis access: a prospective, single-center experience.

Abstract: The purpose of this article is to describe several complex vascular access procedures and the outcomes achieved with them in 24 patients (mean age 60 years) undergoing hemodialysis in whom all other accesses had failed and neither peritoneal dialysis nor transplantation was possible. Patients underwent either a necklace bypass (n = 5), axillary loop (n = 1), contralateral internal jugular vein bypass (n = 6), femorofemoral crossover bypass (n = 1), superficial femoral vein transposition (n = 5), axillary artery to popliteal vein bypass (n = 5), or femoral artery to right atrium bypass (n = 1). All grafts implanted were 6 mm, internally reinforced prostheses made of expanded polytetrafluoroethylene (Gore-Tex Intering Vascular Graft). Postoperatively patients had bimonthly clinical examinations in which the thrill, bruit, skin, cannulation sites, and adequacy of dialysis were reviewed. A bimonthly ultrasound dilution assessment that included estimation of the graft inflow rate, recirculation rate, and cardiac output was also performed. There was one serious postoperative complication: rapid-onset severe steal syndrome that required immediate tie off of the fistula. During the median follow-up time of 22 months, three patients died of causes unrelated to their vascular access. Nineteen dilatations and 10 surgical revisions were done. Primary patency rates were 83%, 63.5%, and 63.5%, respectively, at 6 months, 1 year, and 2 years; secondary patency rates were 91%, 77%, and 77%. Complex vascular access procedures can provide patients some additional good-quality time on hemodialysis.

Ultrapure dialysate: facts and myths.

Abstract: During hemodialysis, blood comes in contact with a large volume of dialysate. Since the purity of dialysate has been linked to acute and long-term complications in hemodialysis patients, the limit of bacterial and endotoxin contamination has been reduced in recent years. Questions have been raised as to whether ultrapure dialysate is required to prevent such complications; in particular, the chronic inflammatory status frequently found in chronically hemodialyzed patients. In vivo and in vitro data suggest that cytokine stimulation in the blood depends on the concentration of bacteria or endotoxin in the dialysate and on the endotoxin permeability of the dialysis membrane. It is not proven whether ultrapure dialysate reduces significantly proinflammatory cytokine generation compared with standard dialysate within the limits of recent recommendations, if rather impermeable dialysis membranes are used. Cuprophane membranes are more permeable to cytokine-inducing substances compared with synthetic membranes such as polysulfone and polyamide. Clinical reports have also attempted to link several acute and chronic complications of hemodialysis to dialysate purity. To date, however, there is no large randomized clinical trial demonstrating that ultrapure dialysate significantly reduces biomarkers of inflammation and other consequential putative complications, including dialysis-related amyloidosis, erythropoietin requirement, and cardiovascular morbidity and mortality. In conclusion, based on the existing clinical data, ultrapure dialysate is recommended in the setting of suboptimal bacteriologic quality of standard dialysate and the use of permeable dialysis membranes.

Managing erythropoietin hyporesponsiveness.

Abstract: The anemia of chronic kidney disease is associated with cardiovascular disease, decreased quality of life, and mortality. The introduction of recombinant human erythropoietin (rHuEPO) has transformed the management of this condition. However, a significant proportion of patients fail to respond to even high doses of rHuEPO. Several factors have been implicated in the hyporesponsiveness to rHuEPO. Iron deficiency, whether absolute or functional, is considered the most important, and maintenance of adequate iron stores reduces rHuEPO requirements among patients on hemodialysis. However, traditional indices of iron that are currently utilized may not reflect iron stores accurately, and there is also increasing concern regarding the potential long-term toxicity of parenteral iron therapy. Infection and inflammation also influence the response to rHuEPO, both by disruption of iron metabolism and by eliciting the release of cytokines that inhibit erythropoiesis. Oxidative stress may contribute to rHuEPO hyporesponsiveness directly by promoting lipid peroxidation in cell membranes, leading to increased erythrocyte fragility and reduced life span and also through its strong association with inflammation. Severe hyperparathyroidism can lead to a reduced number of erythroid progenitor cells. Inadequate dialysis dose, aluminum overload, nutritional factors such as deficiencies of carnitine, vitamin B12, folic acid, and vitamin C can also reduce the efficacy of rHuEPO therapy. Hyporesponsiveness to rHuEPO presents a challenge to both diagnosis and management in an era where optimizing response to rHuEPO is critical both in limiting the burgeoning costs of anemia management and improving clinical outcomes in the dialysis population.

Dialysis-related carnitine disorder.

Abstract: L-carnitine plays an essential role in the beta-oxidation of fatty acids by catalyzing their transport into the mitochondrial matrix. The kidney maintains plasma free L-carnitine levels in the homeostatic range by selective saturable tubular reabsorption. The preferential retention of free L-carnitine over acyl-L-carnitines by the kidney is lost in patients with end-stage renal disease (ESRD). Loss of renal parenchyma as a site of carnitine synthesis, as well as nonselective clearance of L-carnitine by the dialysis procedure lead to dialysis-related carnitine deficiency. Numerous studies investigating whether L-carnitine supplementation will alleviate several dialysis-related symptoms, such as intradialytic hypotension, heart failure, muscle weakness, low exercise capacity, and anemia, have reported conflicting results. Many of these studies suffer from a lack of randomization and control groups, heterogeneity in the administration of L-carnitine, and nonstandardized measures of symptom improvement. More data exist to support the use of L-carnitine in selected anemic dialysis patients with very large erythropoietin requirements in whom extensive examination for reversible causes of anemia was unrevealing.

Vascular calcifications in uremia: old concepts and new insights.

Abstract: The annual mortality rate in uremic patients, corrected for age, sex, and race, is significantly higher than in the general population. This is primarily due to cardiovascular events. Vascular calcifications play a vital role in the development of cardiovascular morbidity and subsequent increased mortality. Vascular calcification affects both vascular intima and media layers and its mechanism remains poorly understood. Over the last few years it has been shown that, in addition to traditional cardiovascular risk factors, disturbances in mineral metabolism in the uremic milieu, calcium-containing phosphate binders, and vitamin D treatment of secondary hyperparathyroidism may contribute to the pathogenesis of vascular calcifications. Other uremia-related risk factors (e.g.increased oxidized low-density lipoprotein cholesterol, uremic toxins, increased oxidative stress, dialysis and dialysate-related factors, hemodynamic overload, hyperhomocysteinemia) may also play a role. In uremic patients, apart from these facilitating factors, decreased levels of endogenous calcification inhibitors such as fetuin-Amatrix Gla protein, osteoprotegerin, and osteopontin have also been associated with increased calcium-phosphate precipitation in extraskeletal tissues. Finally, vascular calcification is the outcome of the active and dynamic balance of procalcifying and anticalcifying influences. For the prevention and treatment of vascular calcifications, it is essential to avoid treatment modalities that lead to calcium overload, achieve good metabolic control, and optimize dialysis.

Interdialytic weight gain: implications in hemodialysis patients.

Abstract: Interdialytic weight gain (IDWG) is an easily measurable parameter in the dialysis unit, routinely assessed at the beginning of the dialysis session. It is used along with clinical symptoms and signs and predialysis blood pressure readings to make decisions regarding the amount of fluid removal during a dialysis session. IDWG is also used as a basis for fluid and salt intake recommendations. However, advising fluid and salt restriction based solely on IDWG may not be appropriate because of its status as a nutritional indicator, as well. Very few studies have been designed to determine the direct effect of IDWG on morbidity and mortality. Any such effect is confounded by residual renal function and various comorbidities, the effects of which might be difficult to separate from those of IDWG. Most attempts to control IDWG have concentrated on requiring patients to reduce fluid and dietary salt intake. Although there does not seem to be a consensus at this point, it is likely that within the lower values of IDWG (less than 5.7% of dry weight), tighter control of fluid and salt intake might not be warranted since these values may reflect higher protein and calorie intake, indicating better nutritional status.

Dialysis modality and dosing strategy in acute renal failure

Abstract: Many fundamental aspects of the management of renal replacement therapy (RRT) in acute renal failure (ARF) remain unresolved. While data from multiple studies support the initiation of RRT, in the absence of other indications, when the BUN has reached a level of approximately 90-100 mg/dl, there are conflicting data regarding the benefit of earlier initiation of renal support. The relative efficacy of the various RRT modalities is uncertain. Despite growing utilization, a survival benefit or greater recovery of renal function has not been demonstrated for continuous renal replacement therapy (CRRT) as compared to conventional intermittent hemodialysis (IHD). Optimal dosing strategies are also poorly defined. While there is increasing evidence that more intensive renal support is associated with better outcomes in ARF, an optimal Kt/Vurea and treatment frequency for IHD remain to be established. Similarly, although data suggest that continuous venovenous hemofiltration (CVVH) should be dosed at no less than 35 ml/kg/hr (postdilution), confirmation of this dosing strategy and validation for other modalities of CRRT are required.

Use of antiepileptic drugs in patients with kidney disease.

Abstract: The number of medications used to treat different types of seizures has increased over the last 10–15 years. Most of the newer antiepileptic drugs (AEDs) are likely to be unfamiliar to many nephrologists. For both the older and newer AEDs, basic pharmacokinetic information, recommendations for drug dosing in patients with reduced kidney function or who are on dialysis, and adverse renal and fluid-electrolyte effects are reviewed. Newer AEDs are less likely to have significant drug–drug interactions than older agents, but are more likely to need dosage adjustment in patients with reduced kidney function. The most common renal toxicities of these drugs include metabolic acidosis, hyponatremia, and nephrolithiasis; interstitial nephritis and other adverse effects are less common. Little is known about the clearance of most of the newer AEDs with high-efficiency hemodialyzers or with peritoneal dialysis. Monitoring of drug levels when available, careful clinical assessment of patients taking AEDs, and close collaboration with neurologists is essential to the management of patients taking AEDs.

Diagnosis and management of sleep apnea syndrome and restless legs syndrome in dialysis patients.

Abstract: Sleep complaints are very common in patients with end-stage renal disease (ESRD) and contribute to their impaired quality of life. Both obstructive and central sleep apnea syndromes are reported more often in patients on dialysis than in the general population. Impaired daytime functioning, sleepiness, and fatigue, as well as cognitive problems, are well known in patients with sleep apnea. Increasing evidence supports the pathophysiological role of sleep apnea in cardiovascular disorders, which are the leading cause of death in ESRD patients. Uremic factors may be involved in the pathogenesis of sleep apnea in this patient population and optimal dialysis may reduce disease severity. Furthermore, treatment with continuous positive airway pressure may improve quality of life and may help to manage hypertension in these patients. Secondary restless legs syndrome is highly prevalent in patients on maintenance dialysis. The pathophysiology of the disorder may also involve uremia-related factors, iron deficiency, and anemia, but genetic and lifestyle factors might also play a role. The treatment of restless legs syndrome involves various pharmacologic approaches and might be challenging in severe cases. In this article we review the diagnosis and treatment of sleep apnea and restless legs syndrome, with a focus on dialysis patients. We also briefly review current data regarding sleep problems after transplantation, since these studies may indirectly shed light on the possible pathophysiological role of uremia or dialysis in the etiology of sleep disorders. Considering the importance of sleep disorders, more awareness among professionals involved in the care of patients on dialysis is necessary. Appropriate management of sleep disorders could improve the quality of life and possibly even impact upon survival of renal patients.

Multiple myeloma in end-stage renal disease.

Abstract: Multiple myeloma is a common cause of chronic kidney disease (CKD). Patients with myeloma-related kidney disease but low levels of serum monoclonal proteins can be diagnosed with symptomatic myeloma in a simplified diagnostic classification. The presence and type of renal disease in myeloma is dependent on the light chain secreted. Treatment has recently changed and now includes the use of thalidomide and bisphosphonates. Thalidomide can cause hyperkalemia and bisphosphonates can cause renal failure in patients with CKD. Their use is not contraindicated, but they should be used with caution. High-dose melphalan with an autologous stem cell transplant is now the standard of care and should not be withheld from patients with CKD, even those on dialysis. This treatment can improve the renal disease, and this is more likely if treatment is started early. In patients with persistent dialysis dependence, renal transplantation can be performed if the patient has a complete remission.

Erythropoietin resistance in the treatment of the anemia of chronic renal failure.

Abstract: Resistance to erythropoietin therapy is a common complication of the modern management of anemia in chronic kidney disease. Iron deficiency, deficiency of other nutrients, toxins, infections, and inadequate dialysis account for the vast majority of episodes of such resistance.

Management of intradialytic hypertension: the ongoing challenge.

Abstract: There is no widely accepted definition of intradialytic hypertension. Arbitrary clinical definitions have included an increase in blood pressure during or immediately after hemodialysis, a rise in blood pressure during the second or third hour of dialysis, and an increase in blood pressure that is resistant to ultrafiltration. To date, no studies have evaluated the prevalence and prognostic importance of intradialytic hypertension. The pathogenesis of intradialytic hypertension is complex and is due in part to extracellular fluid volume expansion, increased cardiac output, activation of the renin-angiotensin system and the sympathetic nervous system, increased circulating vasoactive substances resulting in peripheral vasoconstriction, erythropoietin use, and fluctuations in electrolytes and removal of antihypertensive medications during the dialysis procedure. Management strategies of intradialytic hypertension are based on expert opinion using the pathophysiologic principles described above. We conclude that additional epidemiologic, basic science, and interventional studies are needed to further elucidate the prevalence, prognostic importance, pathophysiology, and potential treatment of intradialytic hypertension.

When heparin causes thrombosis: significance, recognition, and management of heparin-induced thrombocytopenia in dialysis patients.

Abstract: Heparin-induced thrombocytopenia (HIT) is characterized by thrombocytopenia and paradoxical hypercoagulability. HIT occurs when an antibody ("HIT antibody") produced against the complex of heparin and platelet factor 4 (PF4) causes systemic platelet consumption and activation. Nephrologists encounter HIT in the care of end-stage renal disease (ESRD) patients because heparin is a routine anticoagulant in hemodialysis. The incidence of HIT in ESRD appears to be lower than in other clinical settings. However, HIT is equally life threatening in ESRD patients and therefore demands the same prompt recognition and aggressive treatment. Diagnosing HIT requires the detection of HIT antibodies. A functional assay (e.g., [(14)C] serotonin release assay) relies on the patient's HIT antibodies to activate donor platelets at pharmacologic heparin concentrations. The more common antigen assay (e.g., enzyme-linked immunosorbent assay [ELISA]) detects the binding of the patient's HIT antibodies to antigens (e.g., heparin-PF4 complex) in a microtiter well and does not involve platelets. The moment HIT is suspected, heparin should be stopped and an alternative anticoagulant initiated immediately, even before the result of a serologic test becomes available. The advent of several new anticoagulants in the last decade, especially argatroban and bivalirudin, has expanded treatment options for HIT in dialysis patients. This review discusses the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of HIT, with special emphasis on concepts relevant to the care of dialysis patients.

Three controversial issues in extracorporeal toxin removal.

Abstract: The optimal method of extracorporeal removal of many toxic compounds is often a matter of debate. Due to the lack of well-designed studies, we are often left with circumstantial evidence, and we must exercise our best clinical judgment as to whether extracorporeal drug removal is beneficial and if so, by what method. It is clear, however, that rapidity in toxin removal is beneficial. We present three issues dealing with extracorporeal removal of toxins for which there is no definitive answer but which may arise in clinical practice. The first is whether continuous renal replacement therapy (CRRT) is better at removing dialyzable toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is at all useful in treating paraquat poisoning. Finally, is any modality of extracorporeal treatment useful in the treatment of amatoxin poisoning? After a thorough literature review, it is evident that definitive answers are not strikingly apparent. However, extracorporeal treatment in the latter two instances may have potential benefit and may be the only hope for patient survival. Due to the urgent nature of treatment for poisoning, as well as the somewhat obscure nature of these issues, there may never be well-designed evidence-based studies to help guide us. In the meantime, we must continue to use less than ideal evidence and our own experience in dealing with these controversial issues to guide our decision-making process.

Extracorporeal strategies for the removal of middle molecules.

Abstract: Uremic toxins with a molecular weight of less than 500 Da are classified as small nitrogenous waste products. They are highly water soluble, relatively homogeneous, and have no protein binding. Other uremic retention toxins differ significantly from the small nitrogenous metabolite class in molecular weight, heterogeneity, protein binding, and hydrophobicity. The European Uremic Toxin Work Group subdivided molecules into two categories: protein-bound solutes and middle molecules. Middle molecules were defined as toxins in the molecular weight range of 500-60,000 Da, which exceeds the molecular weight of 2000 Da defined in the original middle molecule hypothesis. Under this new proposed definition, most of these middle molecules are low molecular weight peptides and proteins (LMWPs). This concise review focuses on LMWPs. The metabolism of LMWPs is described, including molecular weight, physical conformation, and charge. Factors influencing dialytic removal of LMWPs such as membrane characteristics, protein-membrane interactions, and solute removal mechanisms, as well as strategies to enhance clearance of these compounds are discussed.