Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

[Anemia and iron deficiency in the elderly. Prevalence, diagnostics and new therapeutic options]. / Anämie und Eisenmangel in der Geriatrie. Prävalenz, Diagnostik und neue Therapieoptionen.

The prevalence of anemia in geriatric patients is high. With some variation in different patient cohorts, prevalence of anemia can reach 40%. Anemia is not an age-related disease on its own, but is a symptom with multifactorial genesis and high risk potential. It directly influences mortality, morbidity, and the rate of hospitalization, particularly in older patients suffering from chronic heart failure or chronic kidney disease. The high prevalence of anemia in chronic kidney disease is explained by a combination of erythropoietin and iron deficiency. This review summarizes the recommendations of the iron symposium at the 2010 German Geriatric Society Meeting in Potsdam, Germany. It intends to provide current information on prevalence, diagnostic work-up, and therapeutic options for anemia in the rapidly growing group of elderly patients.

Decorin deficiency in diabetic mice: aggravation of nephropathy due to overexpression of profibrotic factors, enhanced apoptosis and mononuclear cell infiltration.

Although deficiency of the small leucine-rich proteoglycan decorin aggravates diabetic nephropathy in mice, the precise mechanisms of action are not fully understood. In the present study we used decorin-deficient mice (Dcn(-/-)) to further elucidate the molecular mechanisms involved in the protective action of decorin in diabetes. We discovered that streptozotocin-induced diabetes in Dcn(-/-) mice led to increased proteinuria associated with enhanced cyclin-dependent kinase inhibitor p27Kip1 in podocytes and tubular epithelial cells. Furthermore, lack of decorin increased the rate of apoptosis and caused overexpression of the IGF-IR in tubular epithelial cells of diabetic kidneys. In vitro experiments using human proximal renal epithelial cells showed that recombinant decorin was bound to the IGF-IR and protected against high glucose-mediated apoptosis. Furthermore, overexpression of TGFbeta1 and CTGF triggered by decorin deficiency resulted in enhanced accumulation of extracellular matrix in diabetic kidneys. Notably, diabetic Dcn(-/-) kidneys revealed marked upregulation of the proinflammatory proteoglycan biglycan and enhanced infiltration of mononuclear cells. Collectively, our results indicate that decorin is a protective agent during the development of diabetic nephropathy. Future therapeutic approaches that would either enhance the endogenous production of decorin or deliver recombinant decorin to the diseased kidney might improve the outcome of patients with diabetic nephropathy.

Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study.

BACKGROUND: Cinacalcet, a novel calcimimetic, simultaneously lowers parathyroid hormone (PTH), phosphorus (P), calcium (Ca) and Ca x P in patients who are on dialysis with secondary hyperparathyroidism (sHPT) associated with CKD. Previous studies have required cinacalcet to be administered during the dialysis session and at the same time on non-dialysis days. The aim of the SENSOR study was to demonstrate that cinacalcet given in a more clinically practical manner with the first major meal after dialysis is noninferior to cinacalcet given with food during the dialysis session. METHODS: In this open-label study dialysis patients with poorly controlled sHPT (intact PTH (iPTH) (3) 300 pg/ml) were randomized to receive cinacalcet either daily with their post-dialysis meal (n = 337) or with food during the dialysis session (n = 336). The primary endpoint was the proportions of patients with mean iPTH pound 300 pg/ml ( pound 31.8 pmol/l) at Weeks 11 and 13 of a 21-week treatment period. Secondary endpoints included the proportion of patients with Ca x P < 55 mg2/dl2 (< 4.44 mmol2/l2) at Weeks 11 and 13 and patients who discontinued the study due to nausea or vomiting. RESULTS: Comparable proportions of patients in the cinacalcet "during dialysis" and "post-dialysis meal" groups had a mean iPTH pound 300 pg/ml (54 vs. 57%, respectively, 95% confidence interval (CI) difference -4, +10%) and Ca x P < 55 mg2/dl2 (78 vs. 73%, respectively, 95% CI difference -11, +2%) at Weeks 11 and 13. The groups were also comparable at Week 21. Cinacalcet was well tolerated, with < 3% of patients in both groups discontinuing due to nausea or vomiting. A combined post-hoc analysis of both groups showed the incidence of nausea and vomiting was lower if cinacalcet was administered during the evening. CONCLUSIONS: Administering cinacalcet with the first main meal after dialysis was as effective as administration with food during the dialysis session. Cinacalcet was well tolerated. The incidence of gastrointestinal adverse events appeared to be lower when cinacalcet was administered in the evening.

[Current recommendations for the treatment of iron deficiency anemia]. / Recommandations actuelles pour le traitement de l'anémie ferriprive.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/ epoetin alfa) in severe cases. Iron saccharate (VENOFER) is commercially available in Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy: the Dialysis-versus-Diuresis (DVD) Trial.

Contrast medium-induced nephropathy (CIN) is a serious complication with increasing frequency and an unfavorable prognosis. Previous analyses of surrogate parameters have suggested beneficial effects of hemodialysis that are assessed in this randomized clinical trial. We performed a prospective single-center trial in 424 consecutive patients with serum creatinine concentrations between 1.3- 3.5 mg/dl who underwent elective coronary angiography. Patients were randomized to one of three treatment strategies with all patients receiving pre- and postprocedural hydration: One group received no additional therapy, patients in the second group were hemodialyzed once, and the third group received oral N-acetylcysteine. The frequency of CIN (defined as an increase in serum creatinine>or=0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC group (intention-to-treat analysis; P=0.008). There were no differences between the treatment groups with regard to increased (>or=0.5 mg/dl) serum creatinine concentrations after 30-60 days (4.8%, 5.1%, and 3.1%, respectively; P=0.700). Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models of the study groups found quite similar survival rates (P=0.500). In contrast to other (retrospective) studies, long-term survival of patients with vs those without CIN within 72 h was not different, but patients who still had elevated creatinine concentrations at 30-60 days suffered from a markedly higher 2-year mortality (46% vs 17%, P=0.002). In conclusion, hemodialysis in addition to hydration therapy for the prevention of CIN provided no evidence for any outcome benefit but evidence for probable harm. Increased creatinine concentrations at 30-60 days, but not within 72 h, were associated with markedly reduced long-term survival.

[The iron letter--an update on the treatment of iron deficiency anemia]. / Eisenbrief--Aktuelle Empfehlungen zur Therapie der Eisenmangelanämie.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/Epoetin alfa) in severe cases. Iron saccharate Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

[Management of patients with chronic renal failure]. / Die Früherkennung einer Niereninsuffizienz lohnt sich immer. Handeln Sie, bevor das Kreatinin ansteigt.

Terminal renal failure has an incidence of approximately 60 persons per million population, and is on the increase. Victims suffer from an appreciably compromised quality of life and life expectancy. The financial burden on the health service imposed by the need for renal replacement therapy (dialysis or renal transplantation) is considerable. To achieve a therapeutic impact, the underlying kidney disease, as well as the factors driving progression and injury need to be identified as early as possible. Of particular importance in this connection is the rigorous management of arterial hypertension with the use of ACE inhibitors, dietetic measures and normalization of hemoglobin levels.

[Diagnosis and treatment of disordered acid-base balance]. / Diagnostik und Therapie von Störungen des Säure-Basen-Haushalts. Warum Patienten sauer werden.

Differential diagnosis in disordered acid-base homeostasis is usually possible by measuring the pH, pCO2, pO2 and bicarbonate concentration, and enables differentiation between respiratory alkalosis and acidosis, and metabolic alkalosis and acidosis. Compensatory counter-regulation (respiratory or renal) can make correct assessment of the primary disorder problematic. Treatment of the underlying disease, in particular the provision of adequate oxygenation in respiratory disorders is of the essence. In chronic forms of metabolic acidosis, for example in chronic renal insufficiency and elderly patients, bicarbonate substitution should be initiated in order to prevent the negative effects on various organ systems. Sodium bicarbonate formulations that can be assimilated from the small bowel are especially tolerable and suitable.

Iron management in renal failure patients--how do we achieve the best results?

The majority of patients with renal insufficiency suffer from a normochromic, normocytic anaemia. This renal anaemia affects the quality of life of these patients and reduces their chance of survival. Despite the availability of recombinant human erythropoetin for the treatment of renal anaemia, many patients do not achieve the target haemoglobin concentration of more than 11 g/dl. A major factor contributing to suboptimal correction of renal anaemia and reduced responsiveness to epoetin is a lack of iron availability to the stimulated erythropoesis.Thus, forthe majority of patients with renal insufficiency intravenous iron therapy will be the treatment of choice to replete and maintain adequate iron stores.

Amperometric creatinine biosensor for hemodialysis patients.

BACKGROUND: Creatinine is an important clinical laboratory parameter for the evaluation of kidney function. It is essential to determine its concentration in serum of patients suffering from renal insufficiency. During hemodialysis treatment, the measurement of creatinine in the effluent dialysate or ultrafiltrate may give additional information on the efficiency of the extracorporal procedure. Therefore, enzyme sensors with co-immobilized creatinine amidohydrolase, creatine amidinohydrolase and sarcosine oxidase have been used to determine creatinine. METHODS: Enzymatically generated hydrogen peroxide has amperometrically been detected at a platinum-working electrode. To exclude electroactive compounds of the sample matrix, which might interfere with the electrochemical measurement, the sensors have additionally been modified by a Nafion membrane. RESULTS: Such sensors showed a linear detection range of 0.06-1.7 mg/dl for creatinine. Diluting the sample with measuring buffer, it has also been possible to measure pathological creatinine concentrations up to 11 mg/dl. A good correlation between creatinine concentrations in serum, dialysate and ultrafiltrate determined by the presented enzyme sensors and those obtained by both, conventional colorimetric Jaffé and enzymatic measurements have been achieved. CONCLUSION: Further developments will aim at the integration of this measuring principle into the concept to low-cost disposable planar sensors.

Long-term outcome after percutaneous transluminal coronary angioplasty in patients with chronic renal failure with and without diabetic nephropathy.

OBJECTIVE: Percutaneous transluminal coronary angioplasty (PTCA) in patients on maintenance hemodialysis leads to high rates of restenosis and postinterventional complications. The additional influence of diabetes mellitus on the results of PTCA in patients with diabetic nephropathy and reduced but sufficient renal function has not been investigated before. METHODS: In a retrospective case-control study, 51 patients with reduced renal function were compared to 71 matched controls. Patients with elevated creatinine values were divided in two subgroups: diabetic nephropathy (diabetes, n = 15) and stable renal insufficiency (renal failure, n = 36). RESULTS: The control group had normal renal function (creatinine: 1.0 +/- 0.01) and a mean survival time of 3.6 +/- 0.8 years. Patients with renal failure showed a mean survival time of 2.7 +/- 0.3 years (p < 0.001), creatinine values of 2.0 +/- 0.2 and elevated fibrinogen values of 401 +/- 28 (p < 0.01). Patients with diabetes (creatinine: 2.2 +/- 0.2) had a significantly higher mortality rate with a reduced mean survival time of 1.25 +/- 0.3 years (p < 0.001), postinterventional acute renal failure (n = 2, p < 0.01) and Re-PTCA (n = 2, p < 0.05). DISCUSSION: Patients with reduced but stable renal function showed a higher mortality than comparable patients from the control group. The group of patients with diabetic nephropathy has a poor prognosis after PTCA even though renal function was only moderately reduced.

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.

A randomized, controlled parallel-group trial on efficacy and safety of iron sucrose (Venofer) vs iron gluconate (Ferrlecit) in haemodialysis patients treated with rHuEpo.

BACKGROUND: The objectives of the present trial were to compare the efficacy and safety of two i.v. iron preparations with respect to haemoglobin levels, iron status and recombinant human erythropoetin (rHuEpo) dosage requirements in stable, rHuEpo-treated haemodialysis patients (maintenance phase of iron treatment) over 6 months. METHODS: A total of 59 patients were randomized and assigned to one of two treatment groups and 55 patients were analysed (iron sucrose n=27; iron gluconate n=28). Iron sucrose was administered in a dose of 250 mg iron diluted in 100 ml normal saline given over 60 min once per month, while 62.5 mg iron as iron gluconate was given once per week in a slow push injection (5 min). RESULTS: --Efficacy parameters: Haemoglobin levels could be maintained from baseline to endpoint in both groups. There were, however, more patients in the iron sucrose group than in the iron gluconate group for whom treatment was discontinued because their haemoglobin values exceeded 12.5 g/dl or ferritin values exceeded 1000 ng/ml (five vs two and three vs one patient, respectively). Transferrin saturation and serum ferritin increased significantly in both groups (+255.7 ng/ml with iron sucrose and +278.5 ng/ml with iron gluconate), while rHuEpo dosage did not change significantly throughout the study. --Safety parameters: There were a total of 174 infusions of iron sucrose and 720 injections of iron gluconate during the trial; all of them were well tolerated. In particular, we did not observe anaphylactoid reactions or any events suggestive of iron toxicity such as hypotension, dizziness, or nausea. CONCLUSIONS: High doses of iron sucrose (Venofer((R)) at a dose of 250 mg/month) was equally effective in maintaining haemoglobin and equally well tolerated as low doses of iron gluconate (Ferrlecit((R)) at a dose of 62.5 mg once per week) in stable, rHuEpo treated haemodialysis patients.

Renal tolerance of a neutral gadolinium chelate (gadobutrol) in patients with chronic renal failure: results of a randomized study.

PURPOSE: To assess the renal tolerance of 1.0 mol/L gadobutrol as an electrically neutral contrast agent at magnetic resonance (MR) imaging in patients with impaired renal function. MATERIALS AND METHODS: Twenty-one patients with impaired renal function were enrolled in this prospective randomized study and classified into two subgroups according to their creatinine clearance: group 1 (n = 12), less than 80 mL/min (<1.33 mL/sec) and greater than 30 mL/min (>0.50 mL/sec); group 2 (n = 9), less than 30 mL/min (<0.50 mL/sec) and not requiring dialysis. Gadobutrol (1.0 mol/L) was injected intravenously at randomly assigned doses of either 0.1 or 0.3 mmol per kilogram of body weight. Changes in vital signs, clinical chemistry, and urinalysis results, including creatinine clearance, were monitored before, at 6 hours, and then every 24 hours until 72 hours (group 1) or 120 hours (group 2) after intravenous injection of gadobutrol. Hematologic results were checked every other day. RESULTS: No serious adverse event occurred, and no clinically relevant changes in vital signs, hematologic results, clinical chemistry, or urinalysis results were detected in the observation period. Markers for glomerular filtration (creatinine, cystatin C, beta2-microglobulin, creatinine clearance) and tubular function (N-acetyl-beta-D-glucosaminidase, alpha1-microglobulin) were unaffected by gadobutrol in both groups. CONCLUSION: Gadobutrol did not affect renal function and, therefore, proved to be a safe MR contrast agent in patients with impaired renal function. Even in patients with marginal excretory function (creatinine clearance, <30 mL/min [<0.50 mL/sec]), prehydration or treatment with diuretics or hemodialysis are not required after the administration of gadobutrol.

Small proteoglycans in human diabetic nephropathy: discrepancy between glomerular expression and protein accumulation of decorin, biglycan, lumican, and fibromodulin.

Small leucine-rich proteoglycans (SLRPs), for example, decorin, biglycan, fibromodulin, and lumican, are extracellular matrix organizers and binding partners of TGF-b. Decorin is also involved in growth control and angiogenesis. Hence, these proteoglycans are likely of importance in the pathogenesis of diabetic glomerulosclerosis. In normal kidney, SLRPs were preferentially expressed in the tubulointerstitium. Weak expression occurred in the mesangial matrix. Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, by distal tubular cells and in collecting ducts. In all stages of diabetic nephropathy, there was a marked up-regulation of the proteoglycans in tubulointerstitium and glomeruli. Decorin and lumican became expressed in tubuli. However, in glomeruli, overexpression was not mirrored by local proteoglycan accumulation except in advanced nephropathy. In severe glomerulosclerosis, increased decorin concentrations were found in plasma and urine, and urinary TGF-b/decorin complexes could be demonstrated indirectly. The failure to detect an increased glomerular proteoglycan quantity during the development of nephropathy could be explained by assuming that they are secreted into the mesangial matrix, but cleared via the vasculature or the urinary tract, in part as complexes with TGF-b. They could thereby counteract the vicious circle being characterized by increased TGF-b production and increased matrix deposition in diabetic nephropathy.