De novo once-monthly darbepoetin α treatment for the anemia of chronic kidney disease using a computerized algorithmic approach

Background: Anemia of chronic kidney disease (CKD) has been traditionally treated by erythropoiesis-stimulating agents (ESAs) and/or iron following manual determination of dose. We hypothesized that once-monthly (QM) algorithmically dosed darbepoetin α (DA) and iron administration would successfully treat anemia of CKD in ESA-naive CKD subjects. Methods: QM DA and iron doses were determined via a computerized program targeting a hemoglobin (Hb) of 10.5 - 12.5 g/dl in anemic, ESA-naive, CKD Stages 3 - 5 subjects. Six consecutive QM doses were administered. Hb, ferritin, and transferrin saturation were recorded. Data are presented as means ± standard deviation. Results: Anemia was identified in 133 subjects, with a mean follow-up of 188 days. DA doses and Hb were significantly greater at Months 3 and 6 compared to baseline (p \u3c 0.05); DA doses were 109 ± 68 μg and 118 ± 91, respectively, at Months 3 and 6. Hemoglobin levels were correspondingly 11.3 ± 1.1 g/dl and 11.3 ± 1.0. 78% of patients achieved the target Hb by 6 months of therapy. The elevation of Hb was greater in non-proteinuric than proteinuric subjects at 6 months of treatment (11.6 ± 0.8 g/dl vs. 11.0 ± 1.1; p \u3c 0.05), despite lower DA dose (96 ± 76 μg vs. 139 ± 98; p \u3c 0.05). Conclusion: Successful treatment of the anemia of CKD by QM DA based upon a computerized dosing program was achieved by 6 months in 78% of ESA-naïve, CKD subjects. © 2011 Dustri-Verlag Dr. K. Feistle

Different mice inbred strains humoral immune response against human prostate-specific antigen

The aim of the study was an investigation of humoral immune response to prostate-specific antigen (PSA) of different mice inbred strains for further development of recommendations for appropriate immunization schemes for monoclonal antibodies (McAbs) obtaining. The study was conducted using: Balb/c and NZB mice; PSA from human sperm (as immunogen). In case of booster immunization immunogen was previously diluted to the desired concentration (10 or 30 µg per 100 µl) in saline, and injected in the tail vein or intraperitoneally. In case of other immunizations, we prepared emulsion solution of immunogen with adjuvant to final concentration of 10 or 30 µg per 100 µl: PSA was dissolved in saline, the same volume of adjuvant was added, and mixture was thoroughly mixed to form a stable emulsion. When subcutaneous administration, total dose of 100 µl was divided into two equal parts and injected in the hind paw of mice. Intraperitoneal immunization was performed by single administration of 100 µl of emulsion. The level of specific antibodies was determined by titration of blood sera from animals in indirect ELISA. Series of experiments were conducted to determine the level of humoral response of mice of different inbred strains (Balb/c and NZB) for multi-stage immunization with different duration with different amounts of PSA (10 and 30 μg), with different immunoglobulin administration (intraperitoneal and subcutaneously), and with different adjuvants (Freund’s complete and incomplete adjuvants, FCA/FIA). Final booster immunization at a dose of 30 μg was performed either in the same manner as the previous administration of the immunogen, or intravenously in the physio­logical saline solution. Dependencies of the humoral immune response of Balb/c and NZB mice against PSA on the route of administration of immunogen, the dose and duration of immunization were established. It was shown that intraperitoneal administration provided formation of higher titers of specific antibodies in case of both mice strains. Balb/c mice lines more rapidly responded to PSA, than an NZB mice (for all investigated schemes immunization). It was shown that the most effective immunization scheme was three times intraperitoneal administration with 10 µg of PSA for 8 weeks (the first immunization with FCA, and the rest – with FIA) and booster immunogen intravenous administration in saline solution

Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Andrew S Bomback1, James A Tumlin2, Joel Baranski3, James E Bourdeau4, Anatole Besarab5, Alice S Appel1, Jai Radhakrishnan1, Gerald B Appel11Department of Medicine, Division of Nephrology, Columbia University College of Physicians and Surgeons, New York, NY, USA; 2Department of Internal Medicine, Division of Nephrology, University of Tennessee College of Medicine in Chattanooga, Chattanooga, TN, USA; 3Balboa Nephrology Medical Group, San Diego, CA, USA; 4Nephrology Specialists of Oklahoma, Tulsa, OK, USA; 5Department of Medicine, Division of Nephrology and Hypertension, Henry Ford Health System, Detroit, MI, USAPurpose: A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.Patients and methods: Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.Results: Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.Conclusion: ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.Keywords: nephrotic syndrome, membranous nephropathy, chronic kidney diseas

Arterial line pressure control enhanced extracorporeal blood flow prescription in hemodialysis patients

<p>Abstract</p> <p>Background</p> <p>In hemodialysis, extracorporeal blood flow (Qb) recommendation is 300–500 mL/min. To achieve the best Qb, we based our prescription on dynamic arterial line pressure (DALP).</p> <p>Methods</p> <p>This prospective study included 72 patients with catheter Group 1 (G1), 1877 treatments and 35 arterio-venous (AV) fistulae Group 2 (G2), 1868 treatments. The dialysis staff was trained to prescribe Qb sufficient to obtain DALP between -200 to -250 mmHg. We measured ionic clearance (IK: mL/min), access recirculation, DALP (mmHg) and Qb (mL/min). Six prescription zones were identified: from an optimal A zone (Qb > 400, DALP -200 to -250) to zones with lower Qb E (Qb < 300, DALP -200 to -250) and F (Qb < 300, DALP > -199).</p> <p>Results</p> <p>Treatments distribution in A was 695 (37%) in G1 vs. 704 (37.7%) in G2 (<it>P </it>= 0.7). In B 150 (8%) in G1 vs. 458 (24.5%) in G2 (<it>P </it>< 0.0001). Recirculation in A was 10.0% (Inter quartile rank, IQR 6.5, 14.2) in G1 vs. 9.8% (IQR 7.5, 14.1) in G2 (<it>P </it>= 0.62). IK in A was 214 ± 34 (G1) vs. 213 ± 35 (G2) (<it>P </it>= 0.65). IK Anova between G2 zones was: A vs. C and D (<it>P </it>< 0.000001). Staff prescription adherence was 81.3% (G1) vs. 84.1% (G2) (<it>P </it>= 0.02).</p> <p>Conclusion</p> <p>In conclusion, an optimal Qb can de prescribed with DALP of -200 mmHg. Staff adherence to DLAP treatment prescription could be reached up to 81.3% in catheters and 84.1% in AV fistulae.</p

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud analytic framework.\ud Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud performed using Monte Carlo simulation.\ud Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud at higher rates of progression and lower rates of ischemic steal syndrome.\ud Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud before recommending early AVF creation

Maintenance treatment of renal anaemia in haemodialysis patients with methoxy polyethylene glycol-epoetin beta versus darbepoetin alfa administered monthly: a randomized comparative trial

Background. Several studies with erythropoiesis-stimulating agents claim that maintenance therapy of renal anaemia may be possible at extended dosing intervals; however, few studies were randomized, results varied, and comparisons between agents were absent. We report results of a multi-national, randomized, prospective trial comparing haemoglobin maintenance with methoxy polyethylene glycol-epoetin beta and darbepoetin alfa administered once monthly

Optimal and continuous anaemia control in a cohort of dialysis patients in Switzerland

BACKGROUND: Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. METHODS: A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. RESULTS: Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 +/- 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb &amp;gt;or= 11 g/dL. Mean EPO dose was 155 +/- 118 IU/kg/week, being delivered mostly by subcutaneous route (64-71%). Mean serum ferritin and transferrin saturation were 435 +/- 253 microg/L and 30 +/- 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 +/- 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb &amp;gt;or= 11 g/dL than in those with Hb &amp;lt;11 g/dL (19.7% vs 7.3%, p = 0.006). CONCLUSION: In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management

Влияние скармливания телятам заменителя обезжиренного молока на физиологическое состояние и продуктивность

The high demand for protein during this period of the calf's life is due to the active growth of muscle tissue, and protein is the structural material of all organs. A lack of protein in the diet of calves contributes to a delay in their growth and an excess to the expenditure of additional energy for the deamination of excess amino acids and the elimination of the corresponding decay products through the excretory system of the body. The younger the calves, the higher the protein level in their diet should be. The work aimed to establish the most effective protein norms in the composition of skim milk substitutes for calves over 65 days of age. The study of the influence of feeding skims milk substitute on calves' physiological state and productivity was carried out on four groups of bulls. All tested skim milk replacers varied in protein content but were almost the same in all nutritional parameters. The main ingredients of skim milk substitutes (ZOM 1) for calves of group I were, %: milk proteins – 70, vegetable proteins (soy + wheat) – 29, vitamin and mineral complex, probiotic culture – 1. For calves of group II (ZOM 2) used,%: milk proteins – 70, vegetable proteins (soy + wheat protein) – 29, vitamin-mineral complex – 1. protein) – 29, vitamin and mineral complex – 1. Studies have shown that skim milk substitutes in calves feeding, containing 20 and 22 % protein in the composition of KR-2 compound feed 10 % by weight, was reflected in the improvement of the morpho-biochemical design of the blood. At the same time, there is a tendency to an increase in the concentration of total protein in the blood serum by 3.1 and 3.3 % with a decrease in the amount of urea by 3.5 and 5.2 %, which made it possible to increase the average daily gain in live weight to 3.1 % while reducing costs feed and its price by 1.5 and 0.9 percent.Высокая потребность в протеине в этот период жизни телёнка обусловлена активным ростом мышечной ткани и тем, что белок является структурным материалом всех органов. Недостаток протеина в рационе телят способствует задержке их роста, а избыток – тратам дополнительной энергии на дезаминирование избыточного количества аминокислот и выведение соответствующих продуктов распада через выделительную систему организма. Чем моложе телята, тем выше должен быть уровень протеина в его рационе. Целью работы было установить наиболее эффективные нормы протеина в составе заменителей обезжиренного молока для телят старше 65-дневного возраста. Изучение влияния скармливания заменителя обезжиренного молока на физиологическое состояние и продуктивность телята проведено на 4-х группах бычков. Все опытные заменители обезжиренного молока были различными по содержанию протеина, но практически одинаковыми по всем показателям питательности. Основными ингредиентами заменителей обезжиренного молока (ЗОМ 1) для телят I группы были, %: молочные белки – 70, растительные белки (соевый + пшеничный) – 29, витаминно-минеральный комплекс, пробиотическая культура – 1. Для телят II группы (ЗОМ 2) использовали, %: молочные белки – 70, растительные белки (соевый + пшеничный протеин) – 29, витаминно-минеральный комплекс – 1. В III опытной группе скармливали (ЗОМ 3) состоящий из, %: молочного белка – 70, растительных белков (соевый протеин) – 29, витаминно-минеральный комплекс – 1. Исследованиями установлено, что использование в кормлении телят заменителей обезжиренного молока, содержащих 20 и 22 % протеина в составе комбикорма КР-2 10 % по массе отразилось в улучшении морфо-биохимического состава крови. При этом наблюдается тенденция к повышению концентрации общего белка в сыворотке крови на 3,1 и 3,3 % при снижении количества мочевины на 3,5 и 5,2 %, что позволило увеличить среднесуточный прирост живой массы до 3,1 % при снижении затрат кормов и его себестоимости на 1,5 и 0,9 процента