Serum ferritin in chronic kidney disease: reconsidering the upper limit for iron treatment

Intravenous iron treatment in hemodialysis patients improves the response to recombinant human erythropoietin (rHuEPO) and facilitates achievement of targets for hemoglobin and hematocrit. Excessive treatment, however, could expose patients to risks related to iron overload and oxidative stress. Therefore international treatment guidelines generally recommend that intravenous iron be discontinued when serum ferritin is greater than 500-1000 ng/ml. In this article we explore the relevant issues that inform the decisions as to what levels of serum ferritin are used as the upper limit for treatment. We conclude that the current published literature is inadequate for developing evidence-based guidelines. Clinical judgment is critical to properly weigh the risks and benefits of intravenous iron treatment in the context of the individual patient.     

Oxidants and iron in chronic kidney disease

Oxidants derived either from leukocytes in proliferative glomerular nephritis or from resident glomerular cells in nonproliferative glomerulonephritis have been shown to have several biologic effects relevant to chronic kidney disease. These include: the ability of oxidants to damage glomerular basement membrane (GBM) and to directly induce proteinuria; effects that would lead to a fall in the glomerular filtration rate; and effects that would account for the morphologic changes observed in chronic kidney disease. In experimental models the role of oxidants has been demonstrated in both proliferative glomerulonephritis (e.g., anti-GBM antibody disease) as well as experimental models of minimal change disease and membranous nephropathy. Oxidants have also been shown to be an important mediator of the various pathways that have been implicated in diabetic nephropathy. Antioxidants and iron chelators have also been shown to retard functional and morphologic changes observed in progressive kidney disease. Taken together, these experimental studies suggest an important role of oxidants in chronic kidney disease.     

Disease management in chronic kidney disease

Chronic kidney disease (CKD) is a growing health problem of epidemic proportions both in the United States and worldwide. The care of CKD patients, before and after starting dialysis, remains highly fragmented resulting in suboptimal clinical outcomes and high costs, creating a high burden of disease on patients and the health care system. Disease management (DM) is an approach to coordinating care for this complex population of patients that has the promise of improving outcomes and constraining costs. For CKD patients not yet on dialysis, the major goals of a DM program are (1) early identification of CKD patients and therapy to slow the progression of CKD, (2) identification and management of the complications of CKD per se, (3) identification and management of the complications of comorbid conditions, and (4) smooth transition to renal replacement therapy. For those CKD patients on dialysis, focused attention on avoidable hospitalizations is a key to a successful DM program. Multidisciplinary collaboration among physicians (nephrologist, primary care physician, cardiologist, endocrinologist, vascular surgeons, and transplant physicians) and participating caregivers (nurse, pharmacist, social worker, and dietician) is critical as well. There are several potential barriers to the successful implementation of a CKD/end-stage renal disease DM program, including lack of awareness of the disease state among patients and health care providers, late identification and referrals to a nephrologist, complex fragmented care delivered by multiple providers in many different sites of care, and reimbursement that does not align incentives for all involved. Recent experience suggests that these barriers can be overcome, with DM becoming a promising approach for improving outcomes for this vulnerable population.     

Vascular calcification and arterial stiffness in chronic kidney disease: implications and management

Cardiovascular (CV) disease is the commonest cause of mortality in patients with chronic kidney disease (CKD). Vascular calcification (VC), induced by calcium and phosphate excess and uraemia, is a major risk factor and is independently associated with CV events and death. Local and systemic calcium-regulatory proteins as well as inhibitory extracellular factors are involved in the pathogenesis of VC. In CKD the balance becomes dysregulated leading to differentiation of vascular smooth muscle cells into phenotypically distinct osteoblast-like cells with subsequent ossification of the arterial wall. Associated with imbalances in mineral metabolism, VC has intimate interactions with bone mineralization and enhanced bone resorption. Arterial stiffness represents the functional disturbance of VC, with reduced compliance of large arteries, and predominantly results from greater medial calcification. As with VC, arterial stiffness is an independent predictor of CV mortality and patients with CKD have greater arterial stiffness than the general population resulting in the principal consequences of left ventricular hypertrophy and altered coronary perfusion. Both VC and arterial stiffness can be measured through non-invasive techniques involving computed tomography, ultrasound, echocardiography, and pulse wave velocity. Management in CKD is difficult but detection, prevention and treatment is crucial to reduce CV mortality. The optimal control of mineral metabolism, especially hyperphosphatemia with non-calcium based phosphate binders, has been shown to be effective to reduce VC, and attenuation of arterial stiffness, especially with good blood pressure control, can have a favourable effect with regression of left ventricular hypertrophy. The use of bisphosphonates, calcimimetics, vitamin D therapy and newer experimental treatments, as well as nocturnal dialysis, may have potential benefit.     

Proinflammatory effects of iron sucrose in chronic kidney disease

Inflammation is a central component of progressive chronic kidney disease (CKD). Iron promotes oxidative stress and inflammatory response in animals and promotes progressive CKD. Parenteral iron provokes oxidative stress in patients with CKD; however, its potential to provoke an inflammatory response is unknown. In 20 veterans with CKD, 100 mg iron sucrose was administered intravenously over 5 min and urinary excretion rate and plasma concentration of monocyte chemoattractant protein-1 (MCP-1) were measured at timed intervals over 24 h. Patients were then randomized to placebo or N-acetyl cysteine (NAC) 600 mg b.i.d. and the experiment was repeated at 1 week. Iron sucrose markedly increased plasma concentration and urinary excretion rate of MCP-1 at baseline and at 1 week visits (P < 0.0001 for time effect). Urinary excretion peaked at 30 min and plasma concentration at 15 min. Plasma MCP-1 concentration fell from 164 +/- 17.7 to 135 +/- 17.7 pg/ml with NAC, whereas it remained unchanged from 133 +/- 12.5 to 132 +/- 17.7 pg/ml with placebo (P=0.001 for visit x antioxidant drug interaction). There was a reduction in MCP-1 urinary excretion rate from visit 1 to 2. At the baseline visit, the urinary excretion rate averaged 305 +/- 66 pg/min and at the second visit 245 +/- 67 pg/min (mean difference 60 +/- 28 pg/min, P = 0.030). There was no improvement in urinary MCP-1 excretion with NAC. In conclusion, iron sucrose causes rapid and transient generation and/or release of MCP-1 plasma concentration and increases urinary excretion rate, and systemic MCP-1 level but the urinary excretion rate is not abrogated with the antioxidant NAC. These results may have implications for the progression of CKD with parenteral iron.     

Renal failure: implications of chronic kidney disease in the management of the diabetic foot

Foot complications are common in patients with diabetes, however, chronic kidney disease has emerged as an independent risk factor for development of foot lesions in the diabetic population. Apart from peripheral arterial disease, infection, and neuropathy, which are classic factors contributing to development of foot lesions, skin disorders specific to renal failure, impaired wound healing from uremia, and psychosocial issues offer further compounded risk. Consequently, there are high ulceration and amputation rates that are associated with increased morbidity and mortality. In recent studies, foot-care programs with a multidisciplinary approach within dialysis units have demonstrated improved outcomes.     

Issues related to iron replacement in chronic kidney disease

Recent epidemiologic studies show that iron deficiency occurs in the vast majority of patients with chronic kidney disease (CKD). In patients with CKD, increased iron losses and, to a lesser extent, poor oral absorption, can lead to iron-deficiency anemia. Correction of iron-deficiency anemia is preferable by the oral route, however, data on oral iron use are limited in this population. In CKD patients, parenteral iron administered with recombinant human erythropoietin (rHuEpo), is the best potential option for the correction of anemia. Nondextran iron preparations are preferable because of a reduced incidence of serious adverse events. Parenteral iron in CKD patients may not be entirely innocuous and, although commonly used, have not received Food and Drug Administration approval for use in this patient population. Exposure to intravenous (IV) iron may lead to oxidative stress, renal injury, infection, cardiovascular disease, and osteomalacia. Studies are needed to confirm the existence and magnitude of these complications. The current data suggest that the overall risk-benefit ratio favors use of IV iron when compared with untreated or partially treated iron-deficiency anemia.     

Ethical implications of ethnic disparities in chronic kidney disease and kidney transplantation

Chronic kidney disease (CKD) is a major epidemic in underserved and minority populations largely due to excess rates of hypertensive and diabetic kidney disease. Multiple complex socioeconomic barriers to early diagnosis and optimal therapies as well as delayed referral for kidney transplantation have created disparities in CKD care provided to ethnic minorities. Disparities exist in wait list time and kidney transplant rates for Native Americans and blacks, independent of insurance status. Moreover, independent of genetic matching, long-term transplant outcomes in blacks remain significantly lower than all other ethnic groups, suggesting that poorly understood social factors contribute to these survival differences. The existence of these disparities raises ethical concerns of equity and social justice in terms of the allocation of scarce resources. Although current changes in allocation policies will improve some disparities, more efforts are ultimately needed to improve access to care and the overall health and survival for all individuals at risk for CKD, independent of their race, ethnicity, or socioeconomic status.     

Nutritional management of pregnancy in chronic kidney disease

The nutritional management of pregnant adults with chronic kidney disease (CKD) presents the challenge of combining necessary modifications in nutrient requirements for both pregnancy and kidney impairment. The dietitian must follow these women closely to ensure adequate intakes of kilocalories, protein, and specific vitamins and minerals. Combining the suggested energy and protein needs for CKD recommended by the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines with those for the general population seems feasible during pregnancy. Vitamin and mineral requirements are also a combination of those for CKD and pregnancy. Although diets may need to be restricted because of CKD, goals are to have good communication among members of the health-care team to allow the patient optimal nutrition combined with quality medical care.     

Diabetes management issues for patients with chronic kidney disease

Chronic kidney disease is in continuous increase and can be found in up to 23% of patients with diabetes. Glycemic control is difficult to assess and medication therapy for diabetes may require dose adjustments part of the alteration of drug's pharmacokinetics and the insulin resistance which is predicting cardiovascular events. The recommended hemoglobin A1c goal is also lower than 7.0% without hypoglycemia. In this article, we review the therapeutic management of diabetic patients in chronic renal failure stage which is difficult and the ways to control blood glucose. Multidisciplinary approach, which is including management of comorbid diseases, is necessary to provide the optimal care of these patients.     

Building the chronic kidney disease management team

The need to be efficient and the demands for performance-based service are changing how nephrologists deliver care. Chronic kidney disease (CKD) occurs in patients with complex medical and social problems. CKD management requires that multidisciplinary professionals provide patient education, disease management, and psychosocial support. To remain cost-efficient, many physicians are training and supervising midlevel practitioners in the delivery of specialized health care. Specialized care that meets present CKD patient needs is best delivered in a CKD clinic. Three models of CKD clinic are identified: (1) anemia management CKD clinic, (2) the basic CKD clinic, and (3) the comprehensive CKD clinic. Each clinic model is based on critical elements of staffing, billable services, and patient-focused health care. Billable services are anemia-management services, physician services that may be provided by midlevel practitioners, and medical nutrition therapy. In some cases, social worker services may be billable. Building a patient-focused clinic that offers CKD management requires planning, familiarity with federal regulations and statutes, and skillful practitioners. Making services cost-efficient and outcome oriented requires careful physician leadership, talented midlevel practitioners, and billing professionals who understand the goals of the CKD clinic. As Medicare payment reforms evolve, a well-organized CKD program can be well poised to meet the requirements of payers and congressional mandates for performance-based purchasing.     

Variability and reliability of air plethysmographic measurements for the evaluation of chronic venous disease

Purpose: Air plethysmography (APG) has the potential to help evaluate different treatments for the prevention of recurrence of venous ulcers; however, there are little reported data on the variation and reliability of the different parameters. This study aimed to assess the variation in different APG parameters in patients with chronic venous disease and to evaluate the reliability of APG in test-retest situations.Method: Seventeen patients (18 limbs) with chronic venous disease were recruited into this study. Subjects were asked to undergo tests on two occasions, 1 to 6 weeks apart. Three tests were performed at each visit, and three patients had 10 tests performed at one visit. The coefficients of variation were calculated for repeated measurements and test-retest reliability, and the differences between the means of three tests and the 10 tests were also analyzed.Results: The coefficients of variation for the repeated measurements ranged from 7.5% to 27% for the majority of parameters of APG. The differences between the means of three tests and the means of 10 tests were less than 10% in this study. The coefficients of variation of method error were approximately 10% in test-retest measures.Conclusions: This study has shown that evaluations of calf pump function and venous reflux using APG display variations in repeated measurements and in the test-retest measures. The variations found within patients and on retesting patients on different days suggest that APG is very unlikely to be able to detect small changes in the parameters of venous reflux and calf pump function. It is essential to understand the inherent variation of APG measurements when they are used to assess treatments that are designed to improve venous function. (J Vasc Surg 1997;26:638-42.)     

Beta blockers in the management of chronic kidney disease

The sympathetic nervous system modulates renal function through its receptors namely beta1 (cardiac output and renin release), alpha1 (systemic and renovascular constriction), and beta2 renovascular dilation. Sympathetic overactivity is commonly seen in chronic kidney disease (CKD) and is an important contributor to increasing the risk of cardiovascular events as well as increasing renal disease progression. Recent evaluations of drug use in people with CKD shows a remarkably low percentage of patients receiving beta-blockers, especially in more advanced stage CKD when cardiovascular risk is higher. This is in large part due to tolerability of these agents. Moreover, water-soluble beta-blockers such as atenolol and metoprolol are dialyzable and require supplementation to avoid exacerbation of arrhythmias following dialysis. Newer vasodilating beta-blockers have better tolerability and different effects on renal hemodynamics as well as metabolic variables. These effects are related to the relative alpha1-blocking effect of agents such as carvedilol and labetolol, with carvedilol having relatively greater alpha-blocking effects. Few studies evaluate beta-blockers on cardiovascular risk in CKD patients. Studies with carvedilol demonstrate attenuated increases in albuminuria as well as reduction in cardiovascular events in CKD patients with hypertension. This paper reviews the animal and clinical trial data that evaluate beta-blockers in CKD highlighting the vasodilating beta-blockers. It is apparent that greater use of this drug class for blood pressure control would further enhance reduction of risk of heart failure, the most common cause of death in the first year of starting dialysis.