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A risk/benefit analysis of iron supplementation in pre-dialysis advanced chronic kidney disease (CKD) patients has not been conducted. We aim to assess the effectiveness and the safety of iron supplementation in patients with CKD Stage 5 who have not yet received dialysis (CKD 5 ND).A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From 1 January 2000 to 30 June 2009, we enrolled 31 971 adult patients who had a serum creatinine6 mg/dL and a haematocrit28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without iron supplementation within 90 days after starting ESA therapy. Patient follow-up took place until dialysis, death before initiation of dialysis or 31 December 2009. The primary outcomes were death before initiating dialysis, hospitalization before death or long-term dialysis.After propensity score matching, the patients who received iron supplementation were associated with a lower risk of all-cause death [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.80-0.90] compared with non-users. The survival benefit of iron use was consistent across the majority of dosage groups, except for those who were treated with monthly IV iron200 mg. Moreover, compared with the non-users, the iron users were associated with a lower risk of hospitalizations (HR, 0.97; 95% CI, 0.94-0.99) but with a higher risk of faster progression to end-stage renal disease (HR, 1.05; 95% CI, 1.01-1.08).Iron supplementation is associated with 15% risk reduction in death among CKD 5 ND patients who received ESA treatment. Randomized studies are needed to validate this association.

Background. Optimal response to recombinant human erythropoietin (rHuEpo) in haemodialysis (HD) patients requires provision of sufficient available iron. However, a balance between iron requirements and supplements remains a challenge in clinical practice. Reticulocyte parameters, i.e. reticulocyte haemoglobin content (CHr) and reticulocytes in a high-fluorescence intensity region (HFR), have been shown to be accurate predictors of iron-deficient erythropoiesis as compared with traditional markers. Therefore, the aim of this study was to appraise the diagnostic power of these two parameters in the early prediction of response to intravenous iron (IVFE) medications in HD patients receiving rHuEpo. Methods. Sixty-five HD patients with a serum ferritin level of -500 mgul and on rHuEpo therapy for )6 months were enrolled for IVFE supplementation (100 mg iron saccharate three times a week for 4 weeks, then 100 mg every 2 weeks for 5 months). Haemoglobin, haematocrit, serum ferritin, transferrin saturation, reticulocyte count, percentage of hypochromic red cells, CHr and HFR were measured before and following iron supplementation. Response was defined as a rise in haematocrit of )3% anduor a reduction in rHuEpo dose of )30% over the baseline values at the end of the study. Results. Forty-two patients had a dramatic response to IVFE therapy with a 13.5% increase in mean haematocrit and a 38% reduction in rHuEpo dose at the end of the study (P-0.001). This paralleled a statistically significant rise in CHr and HFR (P0.001). Univariate analyses showed that ferritin (P-0.010) and CHr (P-0.001) at baseline, changes in CHr (DCHr2W, P-0.001) and HFR (DHFR2W, P-0.010) at 2 weeks, as well as changes in CHr (DCHr4W, P-0.001) and HFR (DHFR4W, P-0.001) at 4 weeks, strongly correlated with response to IVFE supplementation. Stepwise discriminant analysis disclosed that DCHr4W in conjunction with DHFR4W exhibited an r 2 value of 0.531 (P-0.001) to predict response to IVFE therapy. Analyses by receiver operating characteristic curves and logistic regression further revealed that DCHr4W at a cut-off value of )1.2 pg and DHFR4W of )500uml were more specific to the status of iron-deficient erythropoiesis following IVFE medications. Combined use of the two cut-off values allowed for the highest accuracy in the early prediction of the response toIVFE therapy,with a sensitivity of 96% and a specificity of 100%. Conclusions. Our study shows that changes in CHr and HFR at either 2 or 4 weeks are superior to the conventional erythrocyte and iron metabolism indices and may serve as reliable parameters to detect irondeficient erythropoiesis in HD patients undergoing rHuEpo therapy. During aggressive IVFE treatment, early identification of non-responsiveness and subsequent discontinuation of treatment can avoid the inadvertent iron-related toxicity due to over-treatment.

Background. The aim of this study was to identify the factors determining the circulating soluble transferrin receptor (sTf R) concentrations in haemodialysis (HD) patients on maintenance recombinant human erythropoietin (rHuEpo) treatment. Methods. In a prospective cross-sectional study, 91 chronic HD patients and 18 anaemic controls with normal renal function were recruited. For each subject, blood samples were measured for complete blood count, reticulocyte count, percentage of hypochromic red cells (% HRC), serum ferritin, serum iron, transferrin saturation (TS), serum erythropoietin (sEpo), C-reactive protein (CRP), and sTf R. HD patients received constant rHuEpo doses and basal sEpo was measured P86 h after the last injection. The age, gender, dialysis vintage, and the above-mentioned parameters were used as independent variables and logarithmic sTfR (log10 sTfR) as a dependent variable in the forward stepwise multiple regression model. Results. HD patients were similar to controls regarding haematocrit, serum ferritin, TS, and % HRC, but had significantly lower sTf R, sEpo, and reticulocyte index. Univariate analyses showed that the sTf R level strongly correlated with sEpo (rs0.60, P-0.001) and % HRC (rs0.60, P-0.001), and significantly with serum ferritin (rs0.29, P-0.01), TS (rs0.27, P-0.05), and dose of rHuEpo administered (rs0.27, P-0.05) in HD patients. sTf R also had a positive correlation with haematocrit (rs0.26, P-0.05), red blood cell (RBC) count (rs0.23, P-0.05), and reticulocyte count (rs0.24, P-0.05), but not with CRP (rs0.16, P)0.05). Multivariate regression analysis disclosed that sEpo, HRC, and serum ferritin were the independent predictors of sTf R level. Overall, the model explained 58.8% of the variability in sTfR (R 2 s0.588, P-0.001). Conclusions. Circulating sTf R is a good index of marrow erythropoietic activity in HD patients during rHuEpo treatment. Its level is also independently up-regulated by functional iron deficiency in the process of enhanced erythropoiesis. Our study showed that sTf R levels quantitatively reflect the integrated effects of iron availability, iron reserves, and erythropoietic stimulation.

Provision of sufficient available iron is a prerequisite to ensure the optimal response to recombinant human erythropoietin (rHuEpo). Functional iron deficiency (a state when iron supply is reduced to meet the demands for increased erythropoiesis) is the common cause of rHuEpo hyporesponsiveness in dialysis patients who have normal iron status, even when they are iron-overloaded. Iron supplementation is not justified for this hyporesponsiveness in patients with iron overload due to the potential hazards of iron overload aggravated by intravenous iron therapy. Furthermore, in vivo studies indicated that the promising effect of intravenous iron medication to overcome iron-deficient erythropoiesis is not observed in iron-overloaded haemodialysis (HD) patients. Ascorbic acid, a water-soluble antioxidant as well as a reducing agent, has a number of associations with iron metabolism. Recent research highlights that ascorbic acid can potentiate the mobilization of iron from inert tissue stores and facilitates the incorporation of iron into protoporphyrin in iron-overloaded HD patients being treated with rHuEpo. Interest has turned towards the use of ascorbic acid as an adjuvant therapy in this field. This review focuses on the improvement of rHuEpo response by administration of ascorbic acid and discusses its clinical implications and potential issues for nephrologists.

Background. Creation of a reliable haemoaccess is a critical problem for practicing nephrologists once haemodialysis has been considered. A double-lumen internal jugular-vein catheter is favoured in most cases requiring temporary haemoaccess. However, numerous complications, even lethal ones, may occur with the cannulating procedure. Using ultrasound, we attempted to describe the occult anatomical variations of vessels which may be responsible for complications. Methods. A 'SiteRite' ultrasonographic device was used to inspect the anatomical structure of the internal jugular veins (IJV) in 104 consecutive uraemic patients undergoing creation of internal jugular vein temporary angioaccess. Images of the vessels and demographic data of patients were recorded and analysed. Results. Anatomical variations of the right and left IJVs were found in 19 (18.3%) and 17 (16.4%) uraemic patients respectively. Unilateral IJV variations were found in 18 patients (17.3%) and bilateral variations were discovered in nine patients (8.7%). A total of 27 patients (26.0%) had IJV anatomical variations that might contribute to difficulty in external landmark­ guided IJV cannulation. Conclusions. The external anatomical landmarks for cannulating the IJV are not reliable in about one­ quarter of uraemic patients. An ultrasound survey on the IJV anatomy is recommended for selecting proper puncture site and reducing risks of insertion complica­ tions for IJV dialysis catheters.

Double-lumen haemodialysis catheters are commonly used for temporary venous access in end-stage renal failure patients who require urgent haemodialysis but who do not have mature vascular access. However, catheter dysfunction, such as thrombosis and infection, is not uncommon. Because the replacement of a nonfunctional double-lumen catheter into a new site exposes patients to greater risk of mechanical complications, guide wire exchange of the catheter is an alternative technique to reduce risk, as long as no exitsite or tunnel infection is present w1x. Here, we report a case of accidental migration of a double-lumen catheter fragment into the internal jugular vein during a guide wire exchange. Immediate retrieval of the fragment was successful by way of a percutaneous transfemoral venous approach. Both surgical removal of the intravascular catheter fragment and prolonged hospitalization after surgery were avoided.

A 73-year-old man had been receiving regular haemodialysis initially via arteriovenous fistula for 3 years and had been using a cuffed dual-lumen permanent catheter (HemoStarTM, BardTM, US) for the preceding year due to vascular access failure. He was referred to our hospital owing to an intermittent fever up to 38°C throughout the preceding month. Repeated blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Fever was persistent despite intravenous administration of teicoplanin for 2 weeks. Upon admission, the HemoStarTM was immediately removed and vancomycin was intravenously administered since catheter-related infection was suspected. However, the fever still persisted, and blood cultures and the tip of HemoStarTM were negative for bacteria. Echocardiography showed no evidence of vegetation. By further survey of possible infection, computed tomography of the abdomen revealed a giant left hydronephrosis and hydroureter with thinning of the renal parenchyma (Figure 1a) due to obstruction by a ureteral stone at the fourth lumbar level (Figure 1b). We placed a pig-tailed catheter in the left renal pelvis and drained out 1400 ml of pus-like material, which displayed a positive culture forMRSA. Following adequate pus drainage and antibiotic treatment, his fever subsided dramatically. Tracing back his history, he had stones in the left kidney, which were treated with extracorporeal shock-wave lithotripsy several times. ‘Giant hydronephrosis’ is a rare condition defined by the presence of 1000 ml or more fluid in the collecting system of kidney [1]. The ureteropelvic junction is the most common site for developing giant hydronephrosis [2]. Stones, congenital ureteral narrowing and ureteropelvic tumours are the major causes [2]. Fever was the initial symptom in the present case; however, the definite diagnosis was made 2 months later. This is typical for this type of occult condition. Unless the physician has a high level of suspicion, recognition of giant hydronephrosis may be delayed and further impeded in the presence of end-stage renal failure. To prevent the infectious complications of giant hydronephrosis, it is mandatory to make an early diagnosis whenever possible. In a febrile haemodialysis patient who was refractory to antibiotic treatment, clinical suspicion of pyohydronephrosis should be aroused, especially in a subject having renal stone history.

A 42-year-old woman who was receiving long-term continuous ambulatory peritoneal dialysis (CAPD) for renal failure was admitted to the hospital because of high fever and chills. Five years earlier, she had been diagnosed to have tuberculous (TB) lymphadenitis based on neck lymph-node biopsy and had been treated with rifampicin, isoniazid and ethambutol for 9 months. She remained well until 1 month before admission, when she began to develop fatigue and body-weight loss. On physical examination, the patient’s abdomen was generally tender, with guarding and rebound tenderness. Initial peritoneal fluid cell count was 18uml and then became 300uml with neutrophil predominance on day 3. Peritoneal fluid for Gram stain and acid-fast bacilli smear were negative. Specimens of blood and peritoneal fluid were obtained for culture and empirical antibiotic therapy was started. However, daily fever spikes persisted, with nightly shaking chills and sweats despite changing antibiotics to a combination of vancomycin, ceftazidime and metronidazole for possible septic syndrome. A computed tomographic scan of the abdomen and pelvis showed ascitic fluid, thickening and oedema of the mesentery and omentum, and multiple enlarged lymph nodes. Repeated peritoneal fluid cultures were sterile. The peritoneal catheter was removed and the patient was transferred to haemodialysis. Six weeks after admission, the peritoneal fluid culture grew Mycobacterium tuberculosis, which was found to be sensitive to isoniazid, rifampicin, ethambutol, pyrazinamide and streptomycin on susceptibility testing. The patient was placed on anti-TB medications consisting of isoniazid, rifampicin and pyrazinamide. The patient was readmitted 3 months later, however, with recurrence of fever and pus discharge from the umbilicus. The pus smear was positive with a moderate (2q) amount of acid-fast bacilli present. A fistulogram (Figure 1), performed under fluoroscopy with contrast injection into the umbilical orifice through an 8 Fr. Foley’s catheter, revealed even dispersion of the contrast medium into the peritoneal cavity, suggesting a direct communication. To our knowledge, umbilical fistula formation has never been observed in association with TB peritonitis during CAPD [1]. The umbilicus is the thinnest part of the lower abdomen. As the peritoneal granulomatous inflammation expands due to non-compliance or development of