Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats.

Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure (BP) increases during rHuEPO therapy, observed particularly in persons with a history of hypertension. To determine whether preexisting hypertension enhances BP increases to rHuEPO, BP responses to 2 wk of rHuEPO or placebo were observed in spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto [WKY] rats. In addition, the role of endothelial-released nitric oxide (NO) in BP alterations caused by rHuEPO through i.v. infusions of endothelium-dependent and independent vasoactive agents were indirectly examined. At trial completion, rHuEPO elevated hematocrit, hemoglobin, and mean cell volume more in SHR than in WKY rats (P less than 0.001). Despite the considerable increase in hematocrit, rHuEPO did not alter BP in either strain. An infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, elevated BP more in rHuEPO-treated SHR than in identically treated WKY rats (P less than 0.05). Further, the administration of L-arginine caused a greater decrease in blood pressure in SHR than in WKY rats, independent of treatment condition (P less than 0.01). Because changes in BP with endothelium-independent agents were similar across groups, responses to L-NMMA and L-arginine were specific to the endothelium and probably independent of basal BP. Thus, rHuEPO provoked greater erythropoiesis in SHR than in WKY rats but did not elevate BP. L-NMMA stimulated higher BP in SHR treated with rHuEPO, suggesting a compensatory increase in vasodilatory NO synthesis to protect against a hypertensive effect of the drug in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)     

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.     

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort

Background

The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case–control cohort and test the pertinence of the proposed thresholds.

Methods

A retrospective case–control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3–5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone.

Results

314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48–0.79; and OR 0.72, 95% CI 0.59–0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02–1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60–0.72, p?=?0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60–0.72, p?=?0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64–0.76, p?=?0.526). A 40% and 20% score thresholds were not superior to eGFR?<?15 and 20 mL/min/1.73 m², respectively. A 10% threshold was more specific than an eGFR?<?30 mL/min/1.73 m².

Conclusion

KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

     

Effects of high- vs low-dose native vitamin D on albuminuria and the renin–angiotensin–aldosterone system: a randomized pilot study

International Urology and Nephrology - Residual albuminuria is associated with an increased risk of progression to ESKD. We tested whether a supplementation with native vitamin D could reduce...     

Simultaneous development of lymphoma in recipients of renal transplants from a single donor: donor origin confirmed by human leukocyte antigen staining and microsatellite analysis

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLD) occur in 0.5% to 2.5% of cases in renal-transplant recipients. Epstein-Barr virus (EBV) is usually detected in the tumor cells, suggesting a role for this virus as an agent of B-cell proliferation. It is unusual for patients receiving allografts from the same donor to develop PTLD simultaneously. METHODS: we describe two patients who received renal allografts from the same donor and developed PTLD simultaneously. The presence of EBV in both tumors was confirmed. In this report, the origin of tumor cells was determined by immunohistochemical human leukocyte antigen (HLA) typing and microsatellite analysis. Clonality was studied by immunoglobulin gene rearrangement analysis. RESULTS: Our results suggest that the tumor originated from donor cells in both patients but, because immunoglobulin gene rearrangements were different, this could mean that lymphoid cells proliferate independently in each recipient. CONCLUSIONS: We propose the following pathogenesis: immortalization of passenger B lymphocytes by EBV, proliferation of these cells, and development of PTLD by means of immunosuppression, antigenic stimulation, and HLA mismatch.     

Nephroprotection: how to slow the progression of chronic renal insufficiency?

Most nephropathies are characterized by a progression that may result in end-stage renal failure (ESRF). Apart from the specific treatment implemented when possible, ESRF may be delayed by nephroprotective therapy. Following the definition of the risk factors likely to induce progressive renal disease, the various therapeutic strategies that may play a nephroprotective role are reviewed. The potential results are described with regard to published data, in particular randomised trials, as recommended by the evidence-based medicine principles. Blockade of the renin-angiotensin system plays a major role in terms of nephroprotection. However, this strategy should not replace lifestyle measures and pharmacological treatment of the metabolic disorders associated to nephropathies.     

Salt, hypertension, and public health

A modest albeit significant relationship has been demonstrated in the past years among dietary sodium intake, individual as well as population blood pressure levels, and even possibly increase in blood pressure with ageing. Intervention data are still limited but globally suggest the validity of the concept i.e. that limiting sodium intake could reduce by several mm Hg the blood pressure levels in the population at large and significantly decrease the hypertension prevalence. Insofar the feasibility of such measures is uncertain and most of the data suggest that they are better driven by public health policies than individual efforts.     

Intensifying iron chelating therapy with desferrioxamine using implantable venous access catheters (Port-A-Cath)]

Deferoxamine is still today the only preventive and curative treatment of transfusional hemochromatosis. It must be perfused daily, intravenously or subcutaneously, during several hours. Implantable infusion devices (Port-A-Cath) offer intravenous access, allowing to use higher doses, while avoiding local swelling due to subcutaneous injections. This device was inserted in 7 major thalassemic patients who presented with severe complications of iron overload, including 4 of them with signs of cardiac failure. Ferritinemias of all patients were lowered after intensifying iron chelation: cardiac function improved drastically in 2 patients. Devices were responsible for some complications: occlusion in one patient, local infections in two. This way of administration of desferal seems useful in patients with high ferritinemia and/or organic complications related to hemochromatosis.