L-carnitine supplementation and EPO requirement in children on chronic hemodialysis

L-carnitine supplementation has been the subject of heated discussion in the context of the treatment of pediatric hemodialysis patients. The aim of this study was to analyze the effect of intravenous L-carnitine supplementation on the erythropoetin (EPO) requirement in six pediatric hemodialysis patients. All patients were on intravenous L-carnitine (2.5 g per session for patients >30 kg and 1 g for those <30 kg) for 9 months. The EPO dose was adapted monthly to maintain a target hemoglobin (Hb) level of 11–13 g/dl. Prior to the initiation of L-carnitine supplementation, the EPO requirement was 1.15 ± 0.22 (range 0.37–1.75) μg/kg darbepoetin alpha. Free carnitine (FC) levels were measured before (40.4 ± 4.9 μmol/l), immediately after the 9-month L-carnitine supplementation period (378.5 ± 77.3 μmol/l), and 4 months after withdrawal of L-carnitine (95.6 ± 4.0 μmol/l). After 9 months, the EPO dose was 0.47 ± 0.10 μg/kg (p < 0.002). The Hb levels increased from 12.2 ± 0.97 to 14.0 ± 0.54 g/dl (p < 0.05) within the first 2 months, and the EPO dose was then decreased in a stepwise manner. In conclusion, following intravenous carnitine supplementation, FC levels were higher and persisted longer than expected. This rise was associated with increased Hb levels and decreased EPO requirement. Since controls were missing for this study, prospective long-term multi-center studies on a large number of patients are required to provide solid answers to the controversial question of L-carnitine supplementation in hemodialyzed children.     

Intravenous iron treatment in paediatric chronic kidney disease patients not on erythropoietin

Intravenous (IV) iron treatment reduces erythropoietin (EPO) dose in paediatric haemodialysis patients. The efficacy in paediatric nonhaemodialysis patients is less well established. IV iron is routinely given in our institution to these patients, including some who have not started EPO. The effect of this strategy was examined. Patients with chronic kidney disease (CKD) or peritoneal dialysis (PD) not on EPO were identified. Case notes were reviewed for haemoglobin (Hb), red cell and iron indices for 6 months before and at least 3 months after IV iron. Five patients were identified. Mean age was 13.3 years and mean IV iron (Venofer) dose = 3.1 mg/kg. Median number of doses = 7 (range 3–10). Hb increased significantly after IV iron from 11.4 ± 0.7 to 12.8 ± 1.3 g/dl (p = 0.02). Mean cell volume increased from 87.7±3.4 to 90.1 ± 3.7 fl (p = 0.01), and mean cell Hb remained unchanged: 29.2 ± 1.2 to 29.7 ± 1.0 pg (p = 0.12). Absolute and percentage reticulocyte count remained unchanged. There was no change in iron indices: ferritin 55.1 ± 31.3 to 97.3 ± 46.5 ng/ml (p = 0.3), iron 18.9 ± 6.9 to 18.1 ± 4.2 μmol/l (p = 0.7), transferrin 1.9 ± 1.6 to 2.0 ± 0.1 g/l (p = 1.0), transferrin saturation 35.7 ± 8.1 to 40.3 ± 18.0% (p = 0.5). IV iron slightly improved Hb levels in five paediatric CKD and PD patients not receiving EPO. This strategy may delay the need for EPO treatment and deserves further evaluation.     

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis

We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n = 16) or hemodialysis (HD; n = 8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months. FC levels were measured in plasma and peritoneal dialysate by tandem mass spectrometry. There were no statistically significant changes in lipid levels, hemoglobin, or rhEPO requirements during the course of the study. Fifteen patients (13 PD, 2 HD) had plasma FC levels measured before and after treatment; FC levels increased from 32.1 ± 14.1 μmol/l to 80.9 ± 38.7 μmol/l (P < 0.001). In PD patients, dialysate FC losses increased from 106 ± 78 μmol/day at baseline to 178 ± 119 μmol/day after supplementation. Positive correlations between FC plasma levels and dialysate levels (R = 0.507) or daily excretion (R = 0.603) were found after treatment. In our case series, an oral dose of 20 mg/kg per day of L-carnitine restored FC levels and produced a positive carnitine balance with no significant effects on hematological parameters or lipid profile over a 3-month period. Prolonged treatment duration may be required to obtain significant results.     

Serum uric acid is associated with high blood pressure in pediatric hemodialysis patients

Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were similar in both groups [6.8 ± 0.2 (HD) vs. 6.5 ± 0.3 (PD), p = 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 ± 2.3 (>6.0 mg/dL) vs. 79.3 ± 5.8 mm Hg (≤6.0 mg/dL), p = 0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r = −0.31, p = 0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA level [4.2 ± 0.6% (≤6.0 mg/dL) vs. 4.3 ± 0.3% (>6.0 mg/dL), p = 0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p = 0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 ± 0.2 (No Meds] vs 7.0 ± 0.2 (BP Meds) mg/dL,  p= 0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r = 0.14; p = 0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status.     

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure

Darbepoetin alfa (DA) is a unique long-acting treatment for anaemia in patients with chronic renal failure (CRF). This study assessed the mean dose of DA to achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF children aged 11 years to 18 years. This observational, prospective study was conducted in 39 patients treated with DA. Twenty-nine patients were switched from recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r-HuEPO. Naive patients received initial doses of 0.45 μg/kg of DA. Switched patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1 μg DA). Among the switched patients, 79.3% received dialysis. No naive patients underwent dialysis. Overall, 74% of patients showed increased Hb level, with a mean value of 11.6 ± 1.6 g/dl, using a mean DA dose of 0.63 ± 0.48 μg/kg per week, and 66.7% patients reached the target Hb level. Hb increased in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8, 12.2) g/dl). Higher doses of DA were needed in the “switched” than in the “naive” patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54, 0.92) and 0.34 (95% CI: 0.16, 0.52) μg/kg per week. Our results indicate the doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an effective treatment to stabilise CRF patients at extended dosing intervals. A prospective observational study, on behalf of the French Society for Pediatric Nephrology. Preliminary results of this study were published in part as an abstract and presented as a poster at the European Society of Pediatric Nephrology in Istanbul 11–13 September 2005 and at the ASN Renal Week in Philadelphia (Pennsylvania) 8–13 November 2005.     

Intraperitoneal treatment with darbepoetin for children on peritoneal dialysis

To determine the efficacy and safety of intraperitoneal administration of darbepoetin in children with renal anemia on peritoneal dialysis, we conducted a single-arm, retrospective, two-centre study in which children were treated with intraperitoneal darbepoetin at the end of nightly intermittent peritoneal dialysis. Controls were those children treated with intraperitoneal erythropoietin six months before conversion to darbepoetin. Children were converted with the conversion factor 200 units erythropoietin = 1 μg darbepoetin. Children who started with darbepoetin, started with 0.45 μg/kg/week. Nineteen children entered the study. The mean age was 6.8 years. Eight children were converted from 201 U/kg/week intraperitoneal erythropoietin to 1.0 μg/kg/week intraperitoneal darbepoetin. They were treated for a median period of 31.5 months. Median darbepoetin dose for an adequate erythropoesis over this period was 0.79 μg/kg/week. All 19 children were treated with darbepoetin for a median period of 13.4 months. The median dose for an adequate erythropoesis over this period was 0.63 μg/kg/week. The peritonitis incidence during this study was once every 25.1 months. Three children developed hypertension; one child developed headache. These complications developed after a rapid increase of hemoglobin concentration. Intraperitoneal administration of darbepoetin is effective and safe for children on peritoneal dialysis.     

High serum adiponectin concentration in children with chronic kidney disease

Adiponectin (ADPN) counteracts the inflammatory response of the endothelium, which plays an important role in the development of atherosclerosis in patients with chronic kidney disease (CKD). Data in children with CKD are scarce. We examined serum ADPN concentration in 90 children with various renal disorders: 28 with CKD on conservative treatment (CKD), 21 on regular dialysis treatment (D), and 41 after kidney transplantation (Tx); 27 age-matched healthy children served as controls (C). Body mass index (BMI), estimated glomerular filtration rate (eGFR), lipids, homocysteine, high sensitivity CRP (hsCRP), and systolic blood pressure (SBP) were also measured. Mean serum ADPN concentration was significantly higher in patients with CKD (27.3 μg/ml ±15.0), on D (34.2 μg/ml ±14.9), and after Tx (23.6 μg/ml ±9.5) compared with ADPN levels in C (13.5 μg/ml ±6.1) (p < 0.0001). Serum ADPN concentration was inversely related to BMI (p = 0.001) and SBP (p = 0.004). In the multiple linear regression analysis, only SBP remained independently associated with ADPN plasma levels. Data show that children with CKD have significantly higher serum ADPN, even after Tx. The protective antiarthrosclerotic effect of ADPN may be mediated by lower SBP, a finding that deserves further study.     

Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease

Sickle cell disease (SCD) is associated with a large spectrum of renal abnormalities, one of which, microalbuminuria/proteinuria (MA/P), is a known predictor of end-stage renal disease. We studied 90 children with SCD (57% male; mean age 11.4 ± 5.2 years) to determine the prevalence and examine clinical correlates of MA/P. The average of two spot urine microalbumin-to-creatinine samples obtained 6 months apart was recorded. Medical records were reviewed for demographic and biochemical data. Medication use, resting office blood pressures (BP), vaso-occlusive pain crises (VOC), and monthly transfusions were recorded. Fourteen children (15.5%) had MA/P. Hemoglobin (Hb) levels were significantly lower in the children with MA than in those without MA/P (8.8 ± 1.1 vs. 9.8 ± 1.4 g/dL, respectively) and were significantly correlated with MA (rho = 0.24, p = 0.03). Children with MA were more likely to have abnormal BP (p = 0.058), with 5/14 being hypertensive or pre-hypertensive. In a multivariate logistic regression model of MA, both Hb and BP classification remained in the final model. MA is a simple screening biomarker of early kidney injury in children with SCD. Larger studies to evaluate predictive factors of MA and the relationship to BP are needed.     

Determinants of hemoglobin variability in stable peritoneal dialysis patients

Purpose

Significant within-patient hemoglobin (Hb) level variability is well recognized in particularly hemodialysis patients. Several factors such as hospitalizations, intercurrent diseases and IV iron therapy are found to be related to Hb variability (Hb-var). In this observational study, we aimed to identify predictors and outcome of Hb-var in peritoneal dialysis (PD) patients without hospitalization, intercurrent disease and IV iron therapy during the study period.

Methods

All patients were in the maintenance phase of short-acting erythropoiesis-stimulating agents (ESAs) therapy. The target range of Hb was 11–12 g/dL according to KDOQI Guidelines in 2007. The desired range of Hb was 11–12.5 g/dL. Patients’ demographic and laboratory data were collected at baseline. Atherosclerotic disease was assessed using carotid intima-media thickness (CIMT). We assessed Hb variability with various methods using SD Hb_mean, SD Hb_range and the velocity of Hb change. Hb deflect_positive, Hb deflect_negative, Hb values and ESA dosing were recorded monthly for 6 months.

Results

This study included 50 prevalent PD patients (mean age 46.9 ± 13.7 years, 25 women). The mean velocity of Hb change was negatively correlated with age and positively correlated with frequent ESA dose changes. Higher albumin and residual renal function (RRF) were also positively correlated with Hb deflect_positive. Patients with CIMT ≥0.7 cm had lower SD Hb range compared to CIMT <0.7 cm. Cumulative survival was better in patients with Hb levels consistently ≥10 g/dL compared to patients who had Hb <10 g/dL for at least 1 month. However, Hb-var was not associated with mortality.

Conclusions

In PD patients without hospitalization, intercurrent disease(s) or IV iron therapy, young age, higher albumin or RRF and lower CIMT were associated with greater oscillations in response to ESA therapy. Careful and appropriate ESA dose changes considering these parameters could minimize Hb variability in these patients.     

The oxalate level in ultrafiltrate fluid collected from a dialyzer is useful for estimating the plasma oxalate level in hemodialysis patients

Background Patients on chronic hemodialysis are likely to develop secondary hyperoxalemia. It is, however, difficult to measure plasma oxalate levels. To measure plasma oxalate levels, rapid plasma separation, deproteinization, and acidification are essential in preventing the formation of oxalate and the deposition of calcium oxalate within the test tube. The present study was undertaken to examine whether the oxalate level in dialyzer ultrafiltrate is potentially useful for estimating plasma oxalate levels. Methods In nine patients on chronic hemodialysis, the plasma, after deproteinization with a filter, and the ultrafiltrate from the dialyzer before hemodialysis were acidified to a pH level of less than 3, followed by the measurement of oxalate levels by ion chromatography. Also, oxalate levels were compared between acidified and non-acidified ultrafiltrates from the dialyzer. In the second part of the study, seven patients on chronic hemodialysis receiving erythropoietin therapy, in whom the ferritin level was more than 300 ng/ml and transferrin saturation was less than 25%, were intravenously administered ascorbic acid, 100 mg, three times a week, after each dialysis session to facilitate the utilization of stored iron. This treatment was continued until the serum ferritin level decreased to a level below 300 ng/ml (for 3 months, at a maximum). The oxalate level in the dialyzer ultrafiltrate after this treatment was compared with that before treatment. Results The mean ± SE oxalate level in the dialyzer ultrafiltrate was 45 ± 6 μmol/l, essentially equal to the plasma oxalate level (46 ± 7 μmol/l). The plasma oxalate level had a significant positive correlation with the dialyzer ultrafiltrate oxalate level (plasma oxalate level = 0.99 × dialyzer ultrafiltrate oxalate level + 1.5; r = 0.95; P < 0.0001). The oxalate level in the acidified ultrafiltrate (45 ± 6 μmol/l) did not differ significantly from that in the non-acidified ultrafiltrate (45 ± 6 μmol/l). The mean ± SE duration of ascorbic acid administration was 64 ± 13 days. The hemoglobin level remained unchanged at 9.6 ± 0.4 g/dl, whereas the serum iron level increased significantly, from 34 ± 2 μg/dl to 43 ± 4 μg/dl (P < 0.05), and serum ferritin levels decreased significantly, from 645 ± 219 ng/ml to 231 ± 30 ng/ml after the treatment (P < 0.05). The oxalate level in the acidified ultrafiltrate showed no significant change after ascorbic acid administration (31 ± 8 μmol/l vs 47 ± 7 μmol/l). Conclusions In patients on chronic hemodialysis, the oxalate level in acidified ultrafiltrate from the dialyzer was found to be useful for estimating the plasma level of non-protein-bound oxalate. When administering ascorbic acid to hemodialysis patients, the plasma oxalate level can be monitored using this method.     

Pregnancy Nutritional Indices and Birth Weight After Roux-en-Y Gastric Bypass

Background  Maternal metabolic profile and nutritional course of pregnancy after bariatric interventions is incompletely known. Their impact on birth weight has also not been hitherto addressed. Aiming to document such variables, a retrospective study was undertaken. Methods  Women previously submitted to silastic ring Roux-en-Y gastric bypass, who conceived after 0–5 years (n = 14), were investigated. Intake of selected macro- and micronutrients, representative laboratory measurements, and correlation of these findings with birth weight and time to conception was documented. Results  Mean calorie intake was restricted to about 1,800 kcal/day. Protein (71 ± 17 g/day) and supplementary iron (60 mg/day) were barely adequate, and calcium and vitamin B₁₂ did not meet current recommendations, only folic acid being optimal. Biochemical monitoring reflected these inconsistencies, with occasional low values for serum albumin (4.1 ± 0.4 g/dL), hemoglobin (11.4 ± 1.5 g/dL), iron (78 ± 50 μg/dL) and vitamin B₁₂ (193 ± 102 pg/mL) but not folate. Lipids, glucose, and uric acid were much better than before the anti-obesity intervention. Reduced plasma lipids, glucose, and uric acid were associated with larger birth weight, albeit within the normal range. Conclusions  (1) Anemia as well as additional nutritional deficits during pregnancy were not totally eliminated, despite dietary guidance and micronutrient supplementation; (2) alleviation of metabolic comorbidities was demonstrated, and improved normalization predicted higher birth weight; (3) energy and folate intake was sufficient, but other nutrients probably did not reach ideal levels; (4) recent dietary guidelines for this population represent a step forward, but additional studies are needed.     

Effects of Continuous Erythropoietin Receptor Activator (CERA) in Kidney Transplant Recipients

Erythropoietin-stimulating agents (ESAs) are commonly used to treat anemia in kidney transplant recipients (KTRs). Since 2007, continuous erythropoietin receptor activator (CERA) has been one of the newest recombinant ESAs to treat anemia in dialysis and nondialysis patients with chronic kidney disease. The efficacy of CERA to manage anemia has not been extensively evaluated in KTRs. We evaluated safety, efficacy, and satisfaction among KTRs treated with CERA. We enrolled 19 anemic KTRs (60 ± 9.3 y) who were treated with short-acting ESA for ≥24 weeks. They were shifted to the equivalent dose of CERA and followed for 24 weeks. We measured serum hemoglobin, hematocrit, creatinine, iron, ferritin, and transferrin. To investigate tolerance to and satisfaction with short-acting ESA and CERA, questionnaires were administered to the patients before shifting to CERA and at the end of the follow-up. After 6 months, CERA induced an increase in hemoglobin levels (12.3 ± 0.8 vs 11.2 ± 1.1 g/dL; P = .002, CERA vs short-acting ESA, respectively). In 2 patients treatment was discontinued because the hemoglobin increased to >13 g/dL. No significant differences were observed in serum iron and creatinine between short-acting ESA and CERA throughout the study. The questionnaires showed better compliance to CERA treatment with reduced pain at the injection site, which led subjects to prefer CERA to short-acting ESA. In summary, CERA showed better control of anemia compared with short-acting ESA. It was preferred by the majority of patients, mainly because of the reduced number of monthly injections. Our results demonstrated CERA to be effective, safe, and well tolerated in the management of anemia in KTRs.     

Carbamylated Hemoglobin as an Indicator of Hemodialysis Adequacy and Complications

Carbamylation is an irreversible process of non-enzymatic modification of proteins by the breakdown products of urea. The degree of carbamylation has been proposed as an indicator of the control of uremia by dialysis. Our aim is to study potential determinants of carbamylated hemoglobin (CarbHb) and the relationship between CarbHb with dialysis adequacy and common complications of CRF. The study was carried out on 35 patients with CRF on regular hemodialysis (HD) (group 1), 35 patients with CRF on conservative treatments (group 2), and 35 normal controls (group 3). For all groups complete history, clinical examination, routine laboratory investigations, ECG, efficiency of dialysis for group 1 using KT/V, nerve conduction, resting ECG, and CarbHb level were taken. In HD patients, CarbHb correlates with Kt/V (P < 0.001) and neuropathy (P = 0.004). Mean CarbHb is 129.47 ± 23.50, 88.09 ± 9.41, and 30.7950 ± 1.9395 μg CV/g Hb for groups 1, 2, and 3, respectively. ROC curve CarbHb with resting ECG shows the area under the curve (0.765, 0.718) for group 1 and 2, respectively. ROC curve study for CarbHb and nerve affection shows group area under the curve (0.766, 0.551) for group 1 and 2, respectively. CarbHb is higher in uremia and more with regular HD than in patients under conservative treatment. In HD patients CarbHb correlates with KT/V and can be used as a supportive measure for adequacy of dialysis. The presence of complications like IHD and neuropathy in dialysis patients correlates with CarbHb, which can be used as a marker for the tendency to develop these complications.     

Bone tissue concentrations of ciprofloxacin released from biodegradable screws implanted in rabbits skull

Previously, ciprofloxacin-releasing polylactide/polyglycolide 80/20 (SR-PLGA) screws have proven to be biocompatible with sufficient strength. However, there has been no information about the local concentrations of ciprofloxacin in bone tissue after their implantation. To measure bone concentrations of ciprofloxacin, two screws were implanted in each rabbit, one on either side of the sagittal suture (n = 28 rabbits). Follow-up periods were 2, 4, 8, 16, 24, 52 and 78 weeks. From each rabbit, bone blocks containing one screw were retrieved and used to measure drug concentration. Ciprofloxacin concentration at 2 weeks follow-up was 4.4 ± 4.2 μg/g, 14.1 ± 2.7 μg/g at 4 weeks and 7.6 ± 4.5 μg/g at 8 weeks. Measured concentrations were very low at 16 weeks (mean 0.09 ± 0.04 μg/g) and 24 weeks (mean 0.04 ± 0.02 μg/g). Surprisingly, the concentration was higher again at 1 year (mean 1.3 ± 1.0 μg/g). At 1.5 years, concentration had decreased again (mean 0.8 ± 0.6 μg/g). The drug concentration in bone tissue was higher than minimal inhibitory concentration of ciprofloxacin (Staphylococcus aureus 0.1–1.0 μg/g) at 2, 4, and 8 weeks. Ciprofloxacin-releasing SR-PLGA 80/20 screws could be used clinically for osteofixation and infection treatment in cranial bone.     

The Effect of Roux-en-Y Gastric Bypass on Zinc Nutritional Status

Background Researchers have found that zinc nutritional status in obese and diabetic subjects is altered: low zinc concentrations in plasma and erythrocytes, with high urinary zinc excretion, were observed. This study evaluated the effect of Roux-en-Y gastric bypass (RYGBP) on plasma, erythrocyte and urinary zinc concentration. Methods 22 morbidly obese patients were studied before and 6 months after RYGBP. Fasting blood sample and 24-hour urine were collected in the pre- and postoperative phases. A software analyzed the diet information from 3-day food records after RYGBP. Zinc nutritional status was evaluated by determination of the concentration of this mineral in plasma and erythrocytes, and the urinary excretion of zinc / 24 hours by atomic absorption spectrophotometry. Results The diets consumed by the patients had adequate average concentrations of zinc. Zinc concentration in plasma, erythrocytes and urine were within the values of normality before RYGBP, with mean values of 93.25 ± 19.34 μg/dL, 43.85 ± 7.76 μg Zn/gHb and 583.05 ± 359.30 μg Zn/24 hours, respectively. At 6 months after RYGBP, there was a change in these parameters to 69.82 ± 10.95 μg/dL, 51.80 ± 6.92 μg Zn/gHb, 535.29 ± 216.40 μg Zn/24 hours in the concentration of plasma, erythrocyte and urinary zinc. Conclusion These results suggest that RYGBP promoted, besides change in body composition, an alteration in the zinc plasma and erythrocytes concentrations which in the medium and long term, could cause problems for these patients.     

Normal growth and intravascular volume status with good metabolic control during peritoneal dialysis in infancy

The most demanding patient population on peritoneal dialysis (PD) consists of children under 2 years of age. Their growth is inferior to that of older children and maintaining euvolemia is difficult, especially in anuric patients. In this prospective study reported here, we enrolled 21 patients <2 years of age (mean 0.59 years) at onset of PD and monitored their uremia parameters and evaluated their nutrition. Since no good instrument currently exists for estimating intravascular volume status, we used traditional blood pressure measurements, echocardiography, and N-terminal atrial natriuretic peptide measurements. Growth was compared with midparental height. Metabolic control was good. Long-term hypertension was seen in 43% of the patients, but left ventricular hypertrophy decreased during the study period. Mean weekly urea Kt/V was 3.38 ± 0.66 and creatinine clearance was 49 ± 20 L/week per 1.73 m². Catch-up growth was documented in 57% of the patients during PD. However, these children did not attain their midparental height at the end of PD at a mean age of 1.71 years. Although favorable metabolic control and good growth were achieved during PD, these children lagged in term of their midparental height. We conclude that several instruments are needed for determining the management of intravascular volume status and that the control of calcium–phosphorus status is demanding.     

Peritoneal membrane recruitment in rats: a micro-computerized tomography (μCT) study

The peritoneal contact surface area (PCSA), which represents the area parameter in the mass transfer area coefficient (MTAC), is a crucial marker in the evaluation of peritoneal dialysis effectiveness. However, the capacity to recruit a larger PCSA has only been rarely demonstrated in vivo and, in most cases, changes in MTAC are interpreted as permeability changes and not as surface area variations. Here, we report the use of micro-computerized tomography (μCT) for the measurement of PCSA changes to various fill volumes. Using this three-dimensional imaging method, PCSA was measured in vivo in 26 healthy Wistar rats receiving intraperitoneally increasing fill volumes of peritoneal dialysis solutions: 5 mL (group 1, n = 8), 10 mL (group 2, n = 8) and 15 mL (group 3, n = 10) per 100 g of body weight. A non-ionic iodinated contrast agent was added to the dialysis solution in order to distinguish the intraperitoneal dialysis solutions from soft tissues. The normalized PCSA/weight ratio (cm²/g) increased with fill volume: 1.12 ± 0.10 cm²/g (range 0.98–1.25) in group 1; 1.74 ± 0.08 cm²/g (range 1.64–1.87) in group 2; 2.13 ± 0.09 cm²/g(range 1.90–2.30) in group 3. With this μCT method, PCSA recruited in vivo with a 10 mL/100 g fill volume was in the range 94–107%) of ex vivo total peritoneal surface area (evPSA), as calculated with the Kuzlan’s formula. With a 15 mL/100 g fill volume, the in vivo-measured PCSA, the exchange surface area, surpassed the evPSA (range 113–139%).     

腹膜透析与血液透析患者肾性贫血治疗效果比较

目的比较腹膜透析（peritoneal dialysis,PD）与血液透析（hemodialysis,HD）患者肾性贫血的治疗效果。方法选择尿毒症行肾脏替代治疗患者90例,其中腹膜透析患者41例,血液透析患者49例。患者入组前1个月内均未行肾脏替代治疗、未使用促红细胞生成素（erythropoietin,EPO）、无失血;在肾脏替代治疗开始时加用EPO,比较腹膜透析组（PD组）和血液透析组（HD组）患者治疗前、治疗后第1、2、3个月血红蛋白（hemoglobin,Hb）的变化,以及PD组与HD组治疗后3个月超敏C反应蛋白（high sensitivity C reactive protein,hs—CRP）、血白蛋白（albumin,Alb）、尿素清除指数（Kt／V）的差异。结果治疗前2组的Hb值无统计学差异（P〉O．05或P〉0．01）,治疗后第3个月2组的hs-CRP、Alb、Kt／V值无统计学差异（P〉0．05或P〉0．01）。透析治疗前后比较,PD组治疗后第1、2、3个月的Hb值均较治疗前升高（P〈0．05或P〈0．01）,且治疗后第3个月〉第2个月〉第1个月;HD组治疗后第1、2、3个月的Hb值均较治疗前升高（P〈0．05或P〈0．01）,且治疗后第3个月〉第2个月〉第1个月。PD组治疗后第1、2、3个月EPO的Hb值分别高于HD组,差异具有显著性（P〈0．01）。结论肾脏替代治疗、使用EPO可有效纠正尿毒症患者的肾I生贫血,PD患者使用EP0更有利于肾陛贫血的纠正。     

Hemorrhage-Induced Hepatic Injury and Hypoperfusion can be Prevented by Direct Peritoneal Resuscitation

Background  Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). Methods  Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet–dry ratio). Results  Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 ± 28 μg/mL and aspartate aminotransferase (AST), 234 ± 24 μg/mL; p < 0.05) compared to group 1 (73 ± 9 and 119 ± 10 μg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 ± 9 μg/mL and AST 150 ± 17 μg/mL), and tissue edema was similar to sham. Conclusions  CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function. Presented at the Digestive Disease Week, American Association for the Study of Liver Diseases, Los Angeles, CA, USA, May 2006. No conflicts of interest exist. Grant support: This project was supported by a VA Merit Review grant and by NIH research Grant # 5R01 HL076160-03, funded by the National Heart, Lung, and Blood Institute and the United States Army Medical Resources and Material Command.     

Darbepoetin alfa for the treatment of anemia in children undergoing peritoneal dialysis: a multicenter prospective study in Japan

Background

Darbepoetin alfa (DA) is an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia. Since DA has not been approved by the appropriate Japanese drug regulatory agencies for the indication of renal anemia in children in Japan, we have conducted a multicenter prospective study to determine the efficacy and safety of DA in Japanese children undergoing peritoneal dialysis (PD).

Methods

Pediatric patients subcutaneously receiving rHuEPO were switched to DA treatment for a period of 28 weeks. The conversion to the initial dose of DA was calculated as 1 μg DA for 200 IU rHuEPO, and DA was administered intravenously once every 2 weeks. The target hemoglobin (Hb) concentration was defined as 11.0 to ≤13.0 g/dL. In some patients, the dose of DA was adjusted appropriately to achieve this target level, and/or the dosing frequency changed to once every 4 weeks.

Results

In the 25 patients switched from rHuEPO to DA the mean Hb concentration increased from 9.9 ± 1.0 to 11.1 ± 1.0 g/dL at 8 weeks following commencement of the DA treatment. The target Hb concentration was achieved in 88 % of these patients, and 60 % maintained this target value on completion of the study. The dosing frequency was extended to once every 4 weeks in 60 % of patients. Twenty-four adverse events were noted in 11 of 25 patients (44 %); however, there was no causality between DA and adverse events.

Conclusions

The results of this study suggest that intravenous administration of DA once every 2 or 4 weeks is an effective and safe treatment for renal anemia in Japanese children undergoing PD.