Associations of pretransplant serum albumin with post-transplant outcomes in kidney transplant recipients.

The association between pretransplant serum albumin concentration and post-transplant outcomes in kidney transplant recipients is unclear. We hypothesized that in transplant-waitlisted hemodialysis patients, lower serum albumin concentrations are associated with worse post-transplant outcomes. Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 8961 hemodialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (Odds ratio [OR]), respectively. Patients were 48 ± 13 years old and included 37% women and 27% diabetics. The higher pretransplant serum albumin was associated with lower mortality, graft failure and DGF risk even after multivariate adjustment for case-mix, malnutrition-inflammation complex and transplant related variable. Every 0.2 g/dL higher pretransplant serum albumin concentration was associated with 13% lower all-cause mortality (HR = 0.87 [95% confidence interval: 0.82-0.93]), 17% lower cardiovascular mortality (HR = 0.83[0.74-0.93]), 7% lower combined risk of death or graft failure (HR = 0.93[0.89-0.97]) and 4% lower DGF risk (OR = 0.96[0.93-0.99]). Hence, lower pretransplant serum albumin level is associated with worse post-transplant outcomes. Clinical trials to examine interventions to improve nutritional status in transplant-waitlisted hemodialysis patients and their impacts on post-transplant outcomes are indicated.

Associations of body mass index and weight loss with mortality in transplant-waitlisted maintenance hemodialysis patients.

A body mass index (BMI) below morbid obesity range is often a requirement for kidney transplant wait-listing, but data linking BMI changes to mortality during the waitlist period are lacking. By linking the 6-year (7/2001-6/2007) national databases of a large dialysis organization and the Scientific Registry of Transplant Recipients, we identified 14 632 waitlisted hemodialysis patients without kidney transplantation. Time-dependent survival models examined the mortality predictability of 13-week-averaged BMI, pretransplant serum creatinine as a muscle mass surrogate and their changes over time. The patients were on average 52 ± 13 years old, 40% women and had a BMI of 26.9 ± 6.3 kg/m². Each kg/m² increase of BMI was associated with a death hazard ratio (HR) of 0.96 (95%CI: 0.95-0.97). Compared to the lowest creatinine quintile, the 4th and 5th quintiles had death HRs of 0.75 (0.66-0.86) and 0.57 (0.49-0.66), respectively. Compared to minimal (< ± 1 kg) weight change over 6 months, those with 3 kg- < 5 kg and ≥ 5 kg weight loss had death HRs of 1.31 (1.14-1.52) and 1.51 (1.30-1.75), respectively. Similar associations were observed with creatinine changes over time. Transplant-waitlisted hemodialysis patients with lower BMI or muscle mass and/or unintentional weight or muscle loss have higher mortality in this observational study. Impact of intentional weight change remains unclear.

The new FDA label for erythropoietin treatment: how does it affect hemoglobin target?

The erythropoietin analogs have been an important advance for the treatment of the anemia of kidney disease, resulting in reduced need for blood transfusion and improved quality of life. Recent studies, however, have indicated risks associated with targeting higher levels of hemoglobin (Hb). As a result, in March 2007, the US Food and Drug Administration (FDA) substantially changed prescribing information for these drugs to alert clinicians to these risks. In this review, we consider the recent literature, the change in FDA warnings, and new National Kidney Foundation Anemia Guidelines. Suggestions for new Hb targets during erythropoiesis-stimulating agent treatment are presented.

Catheter use is high even among hemodialysis patients with a fistula or graft.

At any given time, approximately 27% of patients in the United States (US) receive hemodialysis through a permanent catheter. However, this cross-sectional estimate may significantly underestimate the lifetime exposure of patients to hemodialysis catheters, and hence, to the excess risk of the adverse clinical events associated with catheter use. To further clarify catheter use in hemodialysis patients, we identified a cohort of fistula and graft patients in the US Renal Data System using Current Procedural Terminology (CPT) codes. Patients were included if their first hemodialysis was between 1 January 1996 and 31 December 2001, and Medicare was their primary payer. We identified permanent catheter insertions in these patients using CPT codes starting 6 months before their first hemodialysis session (or fistula or graft placement, if earlier), and ending 40 months afterward. Most patients (82%) were >65 years old, 57% were male, and 72% were white. The overall rate of permanent catheter insertions was 44 per 100 patient years, with 57% of patients having at least one catheter insertion. The percent of patients receiving a catheter was similar before (30%) and after (27%) the first fistula or graft placement. Cross-sectional analysis may significantly underestimate the lifetime risk of exposure to hemodialysis catheters. Because catheter use is common even in fistula and graft patients, measures used to prevent adverse events associated with catheter use are important in all patients regardless of current access type.

The National Anaemia Action Council, Inc.: the primary North American resource for anaemia education and research.

The mission of the National Anaemia Action Council, Inc. (NAAC) is to raise the awareness of health care professionals and the public regarding the prevalence, symptoms, consequences and under-treatment of anaemia. This editorial illustrates the goals and objectives of NAAC, and depicts past, present and future educational and research projects and findings. NAAC resources in anaemia-related education and research are described in detail.

Novel erythropoiesis stimulating protein for managing the anemia of chronic kidney disease.

Since its introduction, recombinant human erythropoietin (rHuEPO) has become the standard of care for renal anemia. Because of its relatively short half-life, however, it generally is administered two to three times per week. Darbepoetin alfa (novel erythropoiesis stimulating protein [NESP]) is a longer acting erythropoietic agent that allows less frequent dosing to treat anemia. Decreased dosing frequency should result in enhanced patient compliance and convenience and minimize the burden of frequent administration on staff. NESP is biochemically distinct from rHuEPO, having five N-linked carbohydrate chains (two more than rHuEPO). In animal studies, NESP had a half-life approximately three times longer than rHuEPO and raised hemoglobin effectively when administered less frequently than rHuEPO. NESP has been evaluated in clinical trials of dialysis and chronic kidney disease patients. Pharmacokinetic data confirmed that patients with anemia required less frequent dosing with NESP than rHuEPO. After intravenous administration, the mean elimination half-life of NESP was 25.3 hours versus 8.5 hours for rHuEPO. In patients who are rHuEPO-naive and in patients previously managed with rHuEPO, NESP is as effective as rHuEPO for maintaining hemoglobin concentration when administered intravenously or subcutaneously at a reduced frequency of once weekly or once every other week. NESP is well tolerated and has a safety profile comparable to that of rHuEPO. There have been no reports of antibody formation associated with NESP. NESP is an important new tool for physicians to use in the treatment of anemia of chronic kidney disease.

Daily hemodialysis: challenges and opportunities in the delivery and financing of end-stage renal disease patient care.

Daily/home hemodialysis is the latest technologic advance in the care of end-stage renal disease (ESRD) patients, and promises improved clinical outcomes and quality of life. Should these benefits prove to be true, an increasing number of patients will be interested in this modality of care, raising challenges and opportunities for providers of care and payers, as well as patients themselves. For patients to have access to this and other new forms of technology to treat ESRD, it will be necessary to re-examine the current care delivery and financing systems and reconfigure these so that the incentives of best clinical practice and outcomes are properly aligned with appropriate and sensible cost constraint.

Prevalence and characteristics of individuals with chronic kidney disease in a large health maintenance organization.

This study is designed to estimate the prevalence of and gain further insight into the characteristics of the chronic kidney disease (CKD) population in a large US health maintenance organization (HMO) to better understand the CKD population in the United States overall. Analyses were performed using data from a staff and network model HMO in the southwestern United States with more than 150,000 members per year during 1994 to 1997. The estimated prevalence of CKD in the HMO population varied from 0.4% to 7.1%, depending on the definition of CKD used. Regardless of the definition, CKD was more common in men compared with women and in patients with diabetes mellitus and/or hypertension. Applying the age- and sex-specific prevalence rates in the HMO to the US population in 1990, we estimate there were approximately 9.1 million Americans with at least one elevated sex-specific creatinine (Cr) value and approximately 4.2 million Americans with at least two elevated Cr values separated by 90 days or greater, a more rigorous definition of CKD. From these results, it is apparent that there are a large number of patients in the United States with CKD. Most have not been identified because screening for CKD generally is not performed. Considering the high prevalence of CKD and the high cost and clinical morbidity associated with end-stage renal disease (ESRD), it is clear that CKD is an important public health problem. Early identification of patients with CKD would allow treatment that could slow the progression to ESRD, improve clinical outcomes, and constrain the growth of costs in the ESRD program. The time has come for a structured public and professional educational program to address this serious condition.

Evaluation of disease-state management of dialysis patients.

Dialysis patients are the only Medicare beneficiaries prohibited from joining managed care plans. Concerns have been raised about the ability of such plans to provide the comprehensive care required by patients with this complex condition. However, more than 20,000 dialysis patients belong to such plans because they were enrolled before developing end-stage renal disease (ESRD). Disease-state management, successfully applied to patients with diabetes mellitus and congestive heart failure, is now being used in patients with ESRD. Standardized mortality ratios (SMRs) and standardized hospitalization ratios (SHRs) were calculated for 1998 and 1999 in 1,541 patients enrolled in the RMS Disease Management program of renal disease-state management using US Renal Data System methods. SMRs were 0.643 and 0.806 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). SHRs were 0.620 and 0.503 for 1998 and 1999, respectively, significantly different from 1.0 for both years (P < 0.001). Although additional studies are needed to define the aspects of care that are most important for the outcomes seen, this study shows that favorable outcomes are achievable for this vulnerable patient population within a managed care setting that applies coordinated approaches to care.

Erythropoietin and anemia.

Recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of anemia of chronic renal failure. RHuEPO has been shown to increase survival, decrease hospitalizations, improve brain and cognitive function, and improve quality of life for renal patients. Much has been learned about the normal and pathologic physiology of anemia because rHuEPO has become available to investigators, and this has been widely applied. Additional work is needed in better defining the sites of production of endogenous EPO as well as the nature and control of the oxygen sensor(s) in the kidney. Remaining clinical issues related to this remarkable compound include predicting and overcoming resistance; avoiding iron deficiency; determining the appropriate target hemoglobin; increasing the use strategies such as subcutaneous administration to increase efficiency; and devising a more rational payment scheme.

The current and future state of the ESRD program: a provider roundtable.

The decade of the 1990s have seen substantial consolidation of services in the dialysis industry in the United States. A small number of horizontally and/or vertically integrated companies oversee the care of over two-thirds of dialysis patients. There are many questions regarding this trends as well as the vision of these large organizations regarding the future of the ESRD program. The senior physicians in the four largest such organizations agreed to participate in a provider roundtable to share their thoughts on the following issues: What are the advantages and disadvantages of industry consolidation?; What steps has your organization taken to succeed?; What are the key issues facing this industry in the next decade?; What policy changes by the Federal Government do you anticipate?; What policy changes would you like to see? Although significant differences in specifics are clear in the responses, a recurrent theme relates to how value will be maintained in the program-the balance between high-quality outcomes and the costs of achieving these outcomes. This is clearly the challenge in the years ahead.

Complications of chronic renal insufficiency: beyond cardiovascular disease.

The less rigorous attention to the management of the complications of chronic renal insufficiency (CRI) and its comorbid conditions has potentially tragic consequences. In fact, with early recognition and intervention, many of the complications of CRI and its comorbid conditions can be ameliorated or prevented. We review here the most prevalent, troublesome, and potentially preventable complications and comorbidities of CRI with a view toward developing high-quality, cost-effective strategies for delivering early interventional care. Complications of CRI include malnutrition, anemia, disorders of divalent ion metabolism and osteodystrophy, metabolic acidosis, and dyslipidemia. Important comorbid conditions of CRI are hypertension, diabetes mellitus, and cardiovascular disease. Clinical intuition suggests that early intervention will avert morbidity related to the hypoalbuminemia and other nutritional disorders of CRI, the metabolic acidosis, and the dyslipidemias, but prospective data are lacking at present. Correction of anemia, usually with recombinant human erythropoietin, may be key to the prevention of cardiac disease and other comorbidities of CRI. Incipient disorders of bone and mineral metabolism are managed prospectively using such measures as protein restriction to reduce phosphorus intake, phosphate binders, calcium supplementation, and vitamin D analogues. Hypertension, whatever its original etiology, is clearly an important risk factor for the progression of kidney failure and for the development of diffuse vascular disease; appropriate and aggressive treatment is essential. In patients with diabetic nephropathy, the principles of both primary and secondary prevention have been validated in several large trials of glycemic and blood pressure control. The seeds of these insidious, challenging, and costly comorbid conditions are sown very early in CRI, at a time when they are-in theory-most amenable to intervention. We therefore must be as proactive as possible in the timely implementation of relatively simple therapies that have the potential to prevent some of these adverse outcomes of CRI.