Early referral to the nephrologist and timely initiation of renal replacement therapy: a paradigm shift in the management of patients with chronic renal failure.

The high mortality rate among dialysis patients has spawned investigation into potentially correctable factors that are associated with an increased risk of death. Several studies have demonstrated a strong association between an increased risk of death in dialysis patients and suboptimal delivered dose of dialysis, malnutrition, and non-renal comorbidity. In addition, the use of unsubstituted cellulose dialyzers and reprocessed dialyzers also has been associated with an increased risk of death. Increased attention to these factors has resulted in a significant improvement in patient survival. Nonetheless, the mortality of dialysis patients remains unacceptably high and indicates that other factors may be operative. One of the factors that has thus far received scant attention, but could significantly affect morbidity and mortality in dialysis patients, is the timing and quality of care before initiation of dialysis. Optimal pre-end-stage renal disease care involves early interventions aimed at delaying progression of chronic renal failure, judicious management of uremic complications, timely placement of vascular access, timely initiation of renal replacement therapy, and implementation of educational programs targeted at maximum rehabilitation. Given the fact that early referral to the nephrologist is likely to result in optimal pre-dialysis care, the 1993 National Institutes of Health Consensus Statement on Morbidity and Mortality of Dialysis recommended that referral of a patient to a renal team should occur at a serum creatinine of 1.5 mg/dL in women and 2.0 mg/dL in men. Several investigators also have argued that patients with chronic renal failure who begin dialysis at a relatively "high level of residual renal function" (early start) may have lower morbidity and mortality compared with patients who begin dialysis at a more traditional "low level of renal function" (late start). This hypothesis is based on evidence that declining renal function is associated with malnutrition and that malnutrition at the start of dialysis is associated with poor clinical outcomes. Furthermore, patients are started on dialysis at an endogenous solute clearance that is lower than that accepted as optimum for patients on dialysis. Finally, limited clinical studies have demonstrated the benefit of early initiation of dialysis. Consequently, the Peritoneal Dialysis Adequacy Work Group of the National Kidney Foundation-Dialysis Outcomes Quality Initiative recommends that dialysis be initiated when the weekly renal Kt/Vurea decreases to below 2.0 unless all three of the following criteria are fulfilled: (1) stable or increased edema-free body weight, (2) normalized protein equivalent of total nitrogen appearance greater than 0.8, and (3) absence of clinical symptoms and signs attributable to uremia.

Anemia management in patients with chronic renal insufficiency.

The introduction of recombinant human erythropoietin (rHuEPO) more than a decade ago provided the first effective treatment for the anemia of chronic renal insufficiency (CRI). The use of rHuEPO in the treatment of anemia has been associated with partial regression of left ventricular hypertrophy among both dialysis and nondialysis patients, and has been shown to reduce the frequency of cardiac complications such as congestive heart failure and number of days of hospitalization among dialysis patients. Despite this evidence, the anemia of CRI remains highly prevalent, underrecognized, and undertreated. A number of considerations arise regarding the management of anemia among patients with CRI. In this article, we review the rationale for treatment of anemia, current management practices, proposed treatment strategies, and the economic implications of improved anemia treatment.

Anemia: an early complication of chronic renal insufficiency.

The strong association between anemia and cardiovascular complications among patients with end-stage renal disease suggests that anemia during chronic renal insufficiency (CRI) may also have important consequences. We performed a retrospective cohort study to identify factors associated with severe anemia (hematocrit [Hct] < 30%) and examine anemia management practices in CRI. The CRI cohort was composed of 604 adult patients with elevated serum creatinine levels. There was a direct correlation between predicted glomerular filtration rate and Hct (r = 0.49) and an inverse correlation between serum creatinine level and Hct (r = -0.37). Anemia was noted early in CRI; 45% of patients with serum creatinine levels of 2 mg/dL or less had an Hct less than 36%, and 8% had an Hct less than 30%. During the course of the study, mean Hct decreased from 35.1% +/- 5.6% to 31.8% +/- 5.6%. Iron studies were obtained in only 19% of patients, and among these, the prevalence of iron deficiency (transferrin saturation < 20%) was 54%. Only 30% and 26% of patients were administered recombinant human erythropoietin (rHuEPO) and iron, respectively. Multivariate analyses showed that diabetes as the cause of renal disease, greater serum creatinine level, and having a single nephrology visit were associated with greater odds for the presence of anemia. A lower Hct and having a single nephrology visit were associated with greater odds for rHuEPO use. These results show that anemia begins early in the course of CRI, and management of anemia is suboptimal, even among patients under the care of nephrologists. Educational programs to optimize anemia management among patients with CRI are needed.

Frontiers in Internal Medicine.

Clinical research in Internal Medicine has provided many scientific advances during the past few years. However, the newly generated information overrides the time available to read all of the medical literature regarding advances in Internal Medicine. The goal of this review is to summarize some of the most relevant improvements in clinical practice published over the last few years. From Cardiology to Pulmonology, the authors of this review expose in a succinct way what they and many of their peers consider to be the most transcendental information gathered from thousands of publications. The authors of this review article have attempted to avoid sensationalism by including facts instead of just simply optimistic preliminary findings that can mislead clinicians' decision making. The review is focused on information obtained through well-designed, prospective clinical trials and cohorts where the effectiveness of medical interventions and diagnostic procedures were tested.

KDIGO clinical practice guideline for the care of kidney transplant recipients: a summary

The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the monitoring, management, and treatment of kidney transplant recipients is intended to assist the practitioner caring for adults and children after kidney transplantation. The guideline development process followed an evidence-based approach, and management recommendations are based on systematic reviews of relevant treatment trials. Critical appraisal of the quality of the evidence and the strength of recommendations followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. The guideline makes recommendations for immunosuppression and graft monitoring, as well as prevention and treatment of infection, cardiovascular disease, malignancy, and other complications that are common in kidney transplant recipients, including hematological and bone disorders. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. This summary includes a brief description of methodology and the complete guideline recommendations but does not include the rationale and references for each recommendation, which are published elsewhere.

Spinal epidural abscess in hemodialysis patients: report of three cases and review of the literature.

Spinal epidural abscess (SEA) is a rare infection that can evolve to severe permanent neurologic deficit or death if the diagnosis is delayed. We report three cases of SEA in hemodialysis patients and summarize nine previously reported cases occurring in hemodialysis patients, with detailed comparisons to series of SEA from the general medical literature. Among these 12 patients, hemodialysis catheters and arteriovenous grafts were the major source of infection, in contrast to the usual skin source. Staphylococcus aureus was implicated in all cases, but in one patient Bacteroides fragilis also was isolated from both the resected arteriovenous fistula and the SEA, and Escherichia coli was isolated from the arteriovenous fistula. The classic syndrome of SEA includes fever, backache, and local spinal tenderness, followed by progressive radicular and cord compression signs and symptoms. In this series, back pain and radicular pain were common at presentation, but only a minority had fever, back tenderness, weakness, or leukocytosis. Cerebrospinal fluid was typically abnormal but culture negative, whereas blood and epidural abscess cultures were frequently positive. Plain x-ray films, bone scans, and plain computed tomography scans had low diagnostic yield, and magnetic resonance imaging with gadolinium had a sensitivity of 80%. Only myelography or computed tomography-myelography gave consistently correct diagnoses. The clinical outcome was poor, with one patient deceased and seven with severe weakness or paralysis. Early intervention provided a higher likelihood of good outcome, whereas late intervention and preoperative neurologic deficits portended a poor functional result. Because of the high incidence of bacteremia in hemodialysis patients, we recommend that symptoms of fever, backache, and spinal tenderness be promptly evaluated for SEA before signs or symptoms of cord compression develop. Early recognition and treatment with antibiotics and decompressive laminectomy is generally associated with a better outcome.

Acute renal failure due to lymphomatous infiltration of the kidneys.

Acute renal failure (ARF) is an unusual manifestation of lymphomatous infiltration of the kidneys. In this article, a patient whose initial presentation of lymphoma was the sudden onset of painless hematuria and ARF is described. The absence of other causes of ARF, together with massively enlarged unobstructed kidneys on renal ultrasonography, strongly suggested an infiltrative process. Renal biopsy established the diagnosis of non-Hodgkin's lymphoma. Pulse steroid therapy was associated with rapid improvement of renal function and kidney size, but a moderate degree of tumor lysis syndrome ensued. Further recovery followed with chemotherapy. Whereas widespread infiltration of the kidneys is present in almost one third of patients with lymphoma at autopsy, this rarely causes clinical symptoms. Nevertheless, because it often responds to therapy, lymphomatous infiltration should be suspected in any patient presenting with unexplained ARF and enlarged kidneys, especially in the setting of widespread lymphoma.

Pre-end-stage renal disease care in the United States: a state of disrepair.

Patients with end-stage renal disease (ESRD) experience significant morbidity and mortality. Despite improvements in mortality rates, the life expectancies for dialysis patients are still between 16 and 37% of the age-, gender-, and race-matched U.S. population. One of the factors that thus far has received scant attention, but could significantly contribute to morbidity and mortality among ESRD patients, is the timing and quality of care before initiation of dialysis (pre-ESRD care). Pre-ESRD care involves early detection of progressive renal disease, interventions to retard its progression, prevention of uremic complications, attenuation of comorbid conditions, adequate preparation for renal replacement therapy (RRT), and timely initiation of dialysis. Despite the benefits of pre-ESRD care, recent studies suggest that the quality of pre-ESRD care in the United States is suboptimal. However, indices of quality of pre-ESRD care have been neither clearly defined nor validated. Furthermore, few estimates of the size of the pre-ESRD population are available. This review examines the prevalence of several factors that could reasonably be used to define suboptimal pre-ESRD care, including failure of early detection of renal disease, paucity of interventions to slow its progression, predialysis hypoalbuminemia and severe anemia, suboptimal pre-ESRD education and uninformed choice of modality of RRT, delayed placement of a permanent vascular access, and delayed initiation of RRT. Although the data presented strongly suggest that the quality of pre-ESRD care in the United States is suboptimal, further research is needed for a better definition and validation of indices of quality pre-ESRD care, a more accurate estimate of the size of the pre-ESRD population, examination of the causes of suboptimal pre-ESRD care, and identification of populations at risk for suboptimal pre-ESRD care. This understanding would facilitate development of strategies to improve pre-ESRD care and, eventually, outcomes among patients on RRT.

Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States.

Despite improvements in dialysis care, the mortality of patients with end-stage renal disease (ESRD) in the United States remains high. Factors that thus far have received scant attention, but could significantly affect morbidity and mortality in dialysis patients, are the timing and quality of care before the initiation of dialysis (pre-ESRD). Data from the new version of the Health Care Financing Administration (HCFA) 2728 Form were used to examine the prevalence of and factors associated with hypoalbuminemia, severe anemia, and erythropoietin (EPO) use among 155,076 incident chronic dialysis patients in the United States between April 1, 1995 and June 30, 1997. At initiation of dialysis, the median serum albumin and hematocrit were 3.3 g/dl and 28%, respectively. Sixty percent of patients had a serum albumin below the lower limit of normal and 51% had a hematocrit <28%. Overall, only 23% had received EPO pre-ESRD. Among patients with hematocrit <28%, only 20% were receiving EPO, compared to 27% among patients with hematocrit > or =28%. In a multivariate analysis that adjusted for diabetes, functional status, and demographic, socioeconomic, and geographic factors, the odds ratios for hypoalbuminemia, hematocrit <28%, and lack of EPO use were higher for African-Americans, patients with non-private insurance or no insurance, and patients who were started on hemodialysis. There were also significant differences in odds ratios for these outcomes between different geographic regions in the United States. The high prevalence of pre-ESRD hypoalbuminemia, hematocrit <28%, and lack of EPO use suggests that the quality of pre-ESRD care in the United States is suboptimal. Improvement in pre-ESRD care could potentially improve outcomes among ESRD patients.

Effectiveness of cryosupernatant therapy in refractory and chronic relapsing thrombotic thrombocytopenic purpura.

This report describes objective improvement in two patients with poorly responsive thrombotic thrombocytopenic purpura (TTP) syndromes (with cryosupernatant). The first had a partial response to plasma exchange with whole plasma (fresh frozen plasma; FFP) and responded dramatically when switched to plasma exchange with cryosupernatant replacement. The second had chronic TTP (three relapses in 9 months) that required prolonged courses of exchange with FFP (approximately 1 month each) to achieve remission. Attempts to manage her recurrent TTP with infusion of two units of FFP had been unsuccessful. The latter patient was tried on cryosupernatant infusions (2 units daily) and responded within 4 days. Moreover, she has been in continuous remission for 12 months while receiving 2 units (one to three times per week). These results suggest that cryoprecipitate-poor plasma may offer advantages over whole plasma in the management of both acute and chronic forms of TTP.

Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population.

UNLABELLED: Level of renal function at the initiation of dialysis in the U.S. end-stage renal disease population. BACKGROUND: More than 285,000 individuals in the United States suffer from end-stage renal disease (ESRD) and are treated predominantly by dialysis. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are few data about the level of renal function at the onset of ESRD and no established medical criteria for the initiation of dialysis. METHODS: We report the level of serum creatinine and glomerular filtration rate (GFR) in 90,897 patients who began dialysis in the U. S. between April 1995 through September 1997. Data were obtained from the U.S. Renal Data System. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. RESULTS: The mean (SD) serum creatinine was 8.5 (3.8) mg/dl. The mean (SD) predicted GFR was 7.1 (3.1) ml/min/1.73 m2, with a range from 1 to 42 ml/min/1.73 m2. The proportion of patients with predicted GFR of > 10, 5 to 10, and <5 ml/min/1.73 m2 was 14, 63, and 23%, respectively. The mean predicted GFR was significantly lower among younger patients, women, African Americans, patients with a higher body weight, patients with ESRD because of diseases other than diabetes, uninsured patients, patients who were employed, homemakers or students, and patients selecting hemodialysis. CONCLUSIONS: There is wide variation in renal function at the initiation of dialysis in the U.S. ESRD population, and a substantial fraction of patients start dialysis at very low levels of predicted GFR. Further analyses are needed to examine the factors associated with late initiation of dialysis and its impact on the cost and outcomes of ESRD.

Trends in anemia at initiation of dialysis in the United States.

BACKGROUND: Anemia almost invariably develops in patients with chronic renal insufficiency (CRI) and is associated with a wide range of complications. The anemia of CRI can be effectively treated with recombinant human erythropoietin (rHuEPO). Recent studies suggest that the management of anemia of CRI is suboptimal in the United States. METHODS: We examined the trends in hematocrit and rHuEPO use among all patients who started chronic dialysis therapy between April 1, 1995, and December 31, 1999, from the End-stage Renal Disease Medical Evidence Form 2728 submitted to the Health Care Financing Administration of the United States. Follow-up data containing hematocrit levels after initiation were obtained from the Medicare Part A institutional outpatient dialysis provider claims for 1990 to 1998 prevalent patients. RESULTS: From June 1995 to June 1999, the mean hematocrit at initiation of dialysis increased from 28.1 to 29.3%. Likewise, the annual percentage of patients receiving pre-dialysis rHuEPO increased from 21.8 to 28.1%. Patients receiving predialysis rHuEPO had a higher mean hematocrit than patients without predialysis rHuEPO. The annual percentage of patients with hematocrit <24% fell 6.6% and the percentage with hematocrit > or =30% increased 9.2%. The trend toward higher hematocrit levels has been consistent across all age, gender, and race categories. Older patients, males, whites, and those who selected peritoneal dialysis had higher hematocrit levels than their counterparts. There were significant geographic differences in the prevalence of predialysis rHuEPO use. CONCLUSION: There has been a slight improvement in the management of anemia of CRI in the United States. However, a considerable fraction of patients still have hematocrit levels that are significantly lower than the currently recommended target. Furthermore, improvement in the management of anemia could result in improved clinical outcomes among patients with CRI.

Prevalence, predictors, and consequences of late nephrology referral at a tertiary care center.

Despite improvements in dialysis care, mortality of patients with end-stage renal disease (ESRD) remains high. One factor that has thus far received little attention, but might contribute to morbidity and mortality, is the timing of referral to the nephrologist. This study examines the hypothesis that late referral of patients to the nephrologist might lead to suboptimal pre-ESRD care. Clinical and laboratory data were obtained from the patient records and electronic databases of New England Medical Center, its affiliated dialysis unit (Dialysis Clinics, Inc., Boston), and the office records of the outpatient nephrology clinic. Early (ER) and late (LR) referral were defined by the time of first nephrology encounter greater than or less than 4 mo, respectively, before initiation of dialysis. Multivariate models were built to explore factors associated with LR, and whether LR is associated with hypoalbuminemia or late initiation of dialysis. Of the 135 patients, 30 (22%) were referred late. There were no differences in age, gender, race, and cause of ESRD between ER and LR patients. However, there were significant differences in insurance coverage between these two groups. In the multivariate analysis, patients covered by health maintenance organizations were more likely to be referred late (odds ratio = 4.5) than patients covered by Medicare. Compared to ER, LR patients were more likely to have hypoalbuminemia (56% versus 80%), hematocrit <28% (33% versus 55%), and predicted GFR <5 ml/min per 1.73 m2 (17% versus 40%) at the start of dialysis, and less likely to have received erythropoietin (40% versus 17%) or have a functioning permanent vascular access for the first hemodialysis (40% versus 4%). It is concluded that late referral to the nephrologist is common in the United States and is associated with poor pre-ESRD care. Pre-ESRD care of patients treated by nephrologists was also less than ideal. The patient-, physician-, and system-related factors behind this observation are unclear. Meanwhile, pre-ESRD educational efforts need to target patients, generalists, and nephrologists.