Predictors of iron versus erythropoietin responsiveness in anemic hemodialysis patients.

Anemia protocols for hemodialysis patients usually titrate erythropoietin (ESA) according to hemoglobin and iron according to a threshold of ferritin, with variable response seen. A universally optimum threshold for ferritin may be incorrect, and another view is that ESA and iron are alternative anemia treatments, which should be selected based on the likely response to each. Hemodialysis patients developing moderate anemia were randomised to treatment with either an increase in ESA or a course of intravenous iron. Over 2423 patient-months in 197 patients, there were 133 anemia episodes with randomized treatment. Treatment failure was seen in 20/66 patients treated with ESA and 20/67 patients treated with iron (30.3 vs. 29.9%, p = 1.0). Successful ESA treatment was associated with lower C-reactive protein (13.5 vs. 28.6 mg/L, p = 0.038) and lower previous ESA dose (6621 vs. 9273 µg/week, p = 0.097). Successful iron treatment was associated with lower reticulocyte hemoglobin (33.8 vs. 35.5 pg, p = 0.047), lower hepcidin (91.4 vs. 131.0 µg/ml, p = 0.021), and higher C-reactive protein (29.5 vs. 12.6 mg/L, p = 0.085). A four-variable iron preference score was developed to indicate the more favorable treatment, which in a retrospective analysis reduced treatment failure to 17%. Increased ESA and iron are equally effective, though treatment failure occurs in almost 30%. Baseline variables including hepcidin can predict treatment response, and a four-variable score shows promise in allowing directed treatment with improved response rates.

Hepcidin clearance is associated with erythropoietin requirement in stable hemodialysis patients
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BACKGROUND: The discovery of hepcidin, the hormone regulating iron absorption and transport, has improved the understanding of anemia and erythropoietin treatment. Excessive hepcidin signaling causes anemia in chronic inflammatory conditions by restricting iron delivery to the bone marrow. Hepcidin is normally eliminated in the urine, and the high levels seen in renal failure are thought to contribute to renal anemia and resistance to erythropoietin. METHODS: Clearance of hepcidin by hemodialysis was investigated in this study by measurement of plasma hepcidin before and after a single dialysis session in 204 patients. Results: Dialysis significantly reduced circulating hepcidin (p < 0.001) with median (IQR) clearance 47.7 (34.2 - 61.0)%. Dialytic hepcidin clearance was correlated with spKt/V (R = 0.202, p = 0.006), but not related to session length or membrane flux. There was also a strong correlation between hepcidin clearance and erythropoietin dose (R = -0.193, p = 0.007), sufficient to displace more traditional markers of erythropoietin resistance in a linear regression model, suggesting that increased dialytic removal of hepcidin could improve erythropoietin sensitivity. CONCLUSIONS: Hemodialysis reduces circulating hepcidin. Greater hepcidin clearance, which is related to spKt/V, is strongly associated with reduced erythropoietin requirement. This further implicates hepcidin in the pathogenesis of renal anemia and suggests that hepcidin could be a useful therapeutic target for dialysis patients.
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Increased prevalence of eosinophilia in a hemodialysis population: Longitudinal and case control studies.

Eosinophilia is commonly found in patients with clinical reactions to the hemodialysis circuit. With modern membranes, such reactions have become less common, but they may be under diagnosed in patients with subtle symptoms, in whom the presence of eosinophilia is an important diagnostic feature. Two case reports are presented, along with a hemodialysis study of the frequency and clinical associations of eosinophilia. In three hemodialysis facilities, all current hemodialysis patients with persistent eosinophilia (greater than 1 × 10(9) /L for 3 months) were identified. Control patients without eosinophilia (less than 0.5 × 10(9) /L for 3 months) matched for age, gender, and ethnicity were identified from the same facilities. A historical cohort of patients, dialyzing at the same facilities 5 years ago, was screened for the presence of persistent eosinophilia. From 510 patients, 24 cases of persistent eosinophilia were identified (4.7%). The median eosinophil count was 1.75 × 10(9) /L (range 1.1-7.5 × 10(9) /L). The prevalence in a historical cohort 5 years previously was significantly less at 1.5% (P = 0.046). Compared to controls, patients with eosinophilia were more likely to be on an angiotensin converting enzyme inhibitor (41.7% vs. 12.5%, P = 0.049), had a lower C-reactive protein (10 vs. 24 mg/L, P = 0.02) and were more likely to be using a fistula for access (P = 0.049). Over the following 12 months, there was no difference in the mean number of hospital admission days between cases and controls (7.6 vs. 11.5 days, P = 0.54), and no difference in mortality over 29 months (25.0% vs. 29.2%, P = 1.00). Eosinophilia remains not uncommon in hemodialysis patients, and in most cases reflects allergy to components of the dialysis circuit, which is usually subclinical. The overall prognosis for asymptomatic patients appears to be favourable.

Long-term follow-up of patients randomized to biocompatible or conventional peritoneal dialysis solutions show no difference in peritonitis or technique survival.

Peritonitis remains a common clinical problem for patients on peritoneal dialysis (PD). There are, however, retrospective studies with historical controls that suggest that biocompatible PD solutions may reduce the rates of peritonitis. We conducted a randomized controlled study comparing the use of biocompatible and conventional solutions, accumulating over 7000 patient-months experience. We included peritonitis episodes from patients who discontinued PD during the follow-up period. The study was powered to detect a reduction in the peritonitis rate of over half in the 267 randomized patients in demographically similar groups. There were no intergroup differences in PD technique survival irrespective of whether the outcome was censored for death. Peritonitis-free survival was 26.7 months using conventional compared to 23.1 months using biocompatible PD solutions. The peritonitis rates were also not statistically different when measured in patient-months. Thus, despite the finding of non-randomized studies suggesting benefits of the biocompatible PD solutions, we could not detect any clinically significant advantages in terms of technique survival or peritonitis. Although our study is the largest randomized study comparing different PD solutions to date, we do not exclude the possibility that our results are a consequence of the lack of statistical power. Meta-analysis of randomized control trials in this field is essential.

The role of renal biopsy in women with kidney disease identified in pregnancy.

BACKGROUND: Renal disease may present for the first time in pregnancy, either as symptomatic disease or as a consequence of antenatal screening. The role of antenatal and post-partum percutaneous renal biopsy in the management of such patients is discussed. METHODS: We describe two series of women; the first is a series of 20 women presenting with renal disease of a severity to warrant renal biopsy during pregnancy whilst the second, comprises 75 women who had an initial presentation of renal disease in pregnancy and underwent post-partum renal biopsy. RESULTS: Biopsy during pregnancy revealed a glomerular disorder in 19/20 (95%) with immediate change of management in 9/20 (40%). In 17/20 (85%) there was delivery of a live infant at median gestation of 36 weeks (range 25-40). Follow-up of women [median 103.3 months (2.5-256)] showed 9/20 (45%) had a GFR of <60 ml/min/1.73 m(2) [six at end-stage renal failure (ESRF)] and 3/20 were dead. The majority (62/75; 82.6%) of women undergoing post-partum renal biopsy presented with significant proteinuria (40% pre-eclampsia) during pregnancy not resolving post-partum. A glomerular abnormality was found in 64%. At last follow-up of 47 women [median 51.5 months (range 1-212)], 14 patients (29.7%) had significant proteinuria and 20 (42.6%) had a GFR<60 ml/min/1.73 m(2). Six women (12.7%) had ESRF. CONCLUSIONS: Diagnosis and follow-up of renal disease diagnosed in pregnancy is important as progressive disease occurs in this group. Routine antenatal screening provides a useful diagnostic opportunity to detect asymptomatic renal disease. In a selected sub-group, renal biopsy during pregnancy can be helpful in initiation of correct treatment and allowing progression of pregnancy to fetal viability.

Comparative study illustrating difficulties educating the public to respond to chemical terrorism.

BACKGROUND: In recent years, the perceived threat of chemical terrorism has increased. It is hoped that teaching civilians how to behave during a chemical incident will decrease the number of "worried well" patients at hospitals, reduce secondary contamination, and increase compliance with the instructions of emergency services. The governments of the United Kingdom and Israel sent booklets to every household in their respective countries. In Israel, the civilian population was issued chemical personal protective equipment (CPPE). METHODS: The effectiveness of these public education programs was assessed using a scenario-based questionnaire that was distributed to 100 respondents in Birmingham, UK and Jerusalem, Israel. Respondents were asked how they would behave in three deliberate chemical release scenarios and how they would seek information and help. RESULTS: Only 33% of the UK respondents and 22% of the Israeli respondents recalled reading the government booklets. When asked what they would do after being contaminated in a deliberate release, approximately half of the respondents ranked seeking medical care at a hospital as the most appropriate action. The preferred sources of information in the wake of a chemical strike were (in descending order): radio, television, and the Internet. Approximately half of the respondents would call emergency services for information. Forty-one percent of the UK respondents and 33% of Israeli respondents stated that they either would call or go to the nearest hospital to seek information. CONCLUSIONS: The public information campaigns in both countries have had a limited impact. Many citizens claimed they would self-present to the nearest hospital following a chemical attack rather than waiting for the emergency services. A similar response was witnessed in the Sarin attacks in Tokyo and the 1991 Scud missile attacks in Israel. Current UK doctrine mandates that specialist decontamination teams be deployed to the scene of a chemical release. However, this takes > 1 hour, and it requires at least 30 minutes to don hospital CPPE. Therefore, it is imperative that hospitals are equipped to cope with unannounced self-presenters after a chemical attack. This requires CPPE and protocols that are easier to use.