losartan-potassium and Delayed-Graft-Function

Extended criteria donor (ECD) and donation after circulatory death (DCD) kidneys are at increased risk of delayed graft function (DGF). Experimental evidence suggests that erythropoietin (EPO) attenuates renal damage in acute kidney injury. This study piloted the administration of high dose recombinant human EPO-beta at implantation of ECD and DCD kidneys, and evaluated biomarkers of kidney injury post-transplant.. Forty patients were randomly assigned to receive either rhEPO-b (100,000 iu) (n = 19 in the intervention group, as 1 patient was un-transplantable post randomisation), or placebo (n = 20) in this, double blind, placebo-controlled trial at Manchester Royal Infirmary from August 2007 to June 2009. Participants received either an ECD (n = 17) or DCD (n = 22) kidney. Adverse events, renal function, haematopoietic markers, and rejections were recorded out to 90 days post-transplant. Biomarkers of kidney injury (neutrophil gelatinase-associated lipocalin, Kidney Injury Molecule-1 and IL-18) were measured in blood and urine during the first post-operative week.. The incidence of DGF (53% vs 55%) (RR = 1.0; CI = 0.5-1.6; p = 0.93) and slow graft function (SGF) (32% vs 25%) (RR = 1.1; CI = 0.5-1.9; p = 0.73) respectively, serum creatinine, eGFR, haemoglobin and haematocrit, blood pressure, and acute rejection were similar in the 2 study arms. High dose rhEPO-b had little effect on the temporal profiles of the biomarkers.. High dose rhEPO-b appears to be safe and well tolerated in the early post- transplant period in this study, but has little effect on delayed or slow graft function in recipients of kidneys from DCD and ECD donors. Comparing the profiles of biomarkers of kidney injury (NGAL, IL-18 and KIM-1) showed little difference between the rhEPO-b treated and placebo groups. A meta-analysis of five trials yielded an overall estimate of the RR for DGF of 0.89 (CI = 0.73; 1.07), a modest effect favouring EPO but not a significant difference. A definitive trial based on this estimate would require 1000-2500 patients per arm for populations with base DGF rates of 50-30% and 90% power. Such a trial is clearly unfeasible.. EudraCT Number 2006-005373-22 ISRCTN ISRCTN85447324 registered 19/08/09.

Topics: Acute-Phase Proteins; Aged; Biomarkers; Creatinine; Delayed Graft Function; Double-Blind Method; Erythropoietin; Female; Graft Rejection; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-18; Kidney; Kidney Function Tests; Kidney Transplantation; Lipocalin-2; Lipocalins; Male; Membrane Glycoproteins; Middle Aged; Pilot Projects; Protective Agents; Proto-Oncogene Proteins; Receptors, Virus; Tissue Donors

We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuEPO or placebo. The primary study end point was kidney function 6 weeks after transplantation with secondary end points of incidence of delayed graft function and kidney function 12 months after transplantation. Six weeks or 12 months after transplantation, the difference between estimated glomerular filtration rates was not significant comparing 44 patients who received rHuEPO to 44 patients receiving placebo. There was no significant difference regarding the incidence of delayed graft function (10 of 44 with rHuEPO compared with 14 of 44 on placebo). Protocol biopsies at 6 weeks and 6 months post transplant showed no significant differences in all assessed histological indices. The number and severity of adverse events were comparable between groups, as was patient and graft survival after 12 months. Thus, treatment with high-dose rHuEPO after kidney transplantation, although well tolerated, had no effect on long-term graft function or histology.

Topics: Adolescent; Adult; Aged; Delayed Graft Function; Double-Blind Method; Erythropoietin; Female; Glomerular Filtration Rate; Graft Survival; Humans; Incidence; Kidney Transplantation; Male; Middle Aged; Prospective Studies

Delayed graft function (DGF) is associated with adverse long-term outcomes after deceased-donor kidney (DDK) transplantation. Ischemia-reperfusion injury plays a crucial role in the development of DGF. On the basis of promising animal data, this study evaluated any potential benefits of erythropoietin-alfa (EPO-α) given intra-arterially at the time of reperfusion of renal allograft on the degree of allograft function, as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period.. A prospective, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the influence of EPO-α administered intraoperatively on the outcomes of DDK transplantations performed at the study center between March 2007 and July 2009.. Seventy-two patients were randomly assigned to EPO-α (n=36) or placebo (n=36). The incidences of DGF, slow graft function, and immediate graft function did not significantly differ between the treatment and control groups (41.7% versus 47.2%, 25.0% versus 36.1%, and 33.3% versus 16.7%, respectively; P=0.24). The groups had similar levels of urinary biomarkers, including neutrophil gelatinase-associated lipocalin and IL-18 at multiple times points soon after transplantation; urinary output during the first 3 postoperative days; 1-month renal function; and BP readings, hemoglobin, and adverse effects during the first month.. This study did not show any clinically demonstrable beneficial effects of high-dose EPO-α given intra-arterially during the early reperfusion phase in DDK transplant recipients in terms of reducing the incidence of DGF or improving short-term allograft function.

Topics: Acute-Phase Proteins; Adult; Aged; Analysis of Variance; Biomarkers; Blood Pressure; Chi-Square Distribution; Creatinine; Delayed Graft Function; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Incidence; Injections, Intra-Arterial; Interleukin-18; Kidney Transplantation; Lipocalin-2; Lipocalins; Male; Middle Aged; Pennsylvania; Prospective Studies; Proto-Oncogene Proteins; Recombinant Proteins; Reperfusion Injury; Time Factors; Treatment Outcome; Young Adult

Erythropoietin promotes nephroprotection in animal models of ischemia-reperfusion injury. Neorecormon and Prevention of Delayed Graft Function (Neo-PDGF) is a French open-label multicenter randomized study to evaluate the effect of high doses of epoetin beta (EPO-beta) during the first 2 weeks of renal transplantation on renal function in patients at risk for delayed graft function (DGF). One hundred and four patients were included in the study. Patients randomized in treatment group (A) received four injections of EPO-beta (30.000 UI each), given before surgery and at 12 h, 7 days and 14 days posttransplantation. Patients randomized in control group (B) did not receive EPO-beta. Immunosuppression included induction with basiliximab and maintenance therapy with steroids, mycophenolate mofetil and tacrolimus. At 1 month posttransplant, the estimated glomerular filtration rate (MDRD formula) was 42.5 +/- 19.0 mL/min in the EPO-beta group and 44.0 +/- 16.3 mL/min in the control group (p = ns). The frequency of DGF was similar in both groups (32% vs. 38.8%; p = ns). No difference in the incidence of serious adverse events was observed. (ClinicalTrials.gov number, NCT00815867.).

Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal; Basiliximab; Blood Pressure; Body Mass Index; Creatinine; Delayed Graft Function; Erythropoietin; Female; France; Glomerular Filtration Rate; Graft Rejection; Hemoglobins; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Platelet-Derived Growth Factor; Recombinant Fusion Proteins; Recombinant Proteins; Renal Dialysis; Safety; Tacrolimus

Renal transplantation is accompanied by restoration of renal function and endogenous erythropoietin production. The purpose of this study was to investigate the time-related changes of endogenous erythropoietin secretion in the early renal post-transplant period and the influence of various parameters to this process.. Fifty-eight patients were enrolled in the study and followed up for 3 months after successful renal transplantation. Erythropoietin levels were measured at regular intervals and correlated with renal function, cold ischemia time and immunosuppressive regimen used.. Two peaks of serum erythropoietin levels were observed: an early peak that occurred within two days after transplantation and a late one, between weeks 2 and 4, which resulted in increased blood hemoglobin levels. Factors that were found to correlate with erythropoietin levels were delayed graft function, cyclosporine use and prolonged cold ischemia time. Serum creatinine did not correlate to erythropoietin levels although the reduction of serum creatinine preceded the rise of erythropoietin levels. Normal hemoglobin values were restored about three months after successful renal transplantation.. Serum erythropoietin levels increase during the early post-transplantation period resulting in correction of anemia three months after a successful renal transplantation. Restoration of allograft function is a prerequisite for erythropoietin secretion, while cold ischemia time and immunosuppressive regimen affect graft function.

Topics: Adult; Delayed Graft Function; Erythropoietin; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Period; Retrospective Studies; Time Factors; Transplant Recipients; Young Adult

Topics: Aged; Anemia, Hemolytic; Antibodies, Monoclonal, Murine-Derived; Darbepoetin alfa; Delayed Graft Function; Diagnosis, Differential; Erythropoietin; Female; Graft vs Host Disease; Hematinics; Hemolysis; Hemolytic-Uremic Syndrome; Humans; Immunologic Factors; Kidney Failure, Chronic; Kidney Transplantation; Rituximab