Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury
BACKGROUND Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.
Hospitalized patients enrolled across four countries in the Informing Fresh versus Old Red Cell Management (INFORM) trial (n= 14,461).
Transfusion with freshest available erythrocyte units (n= 4,777).
Transfusion with oldest available erythrocyte units (n= 9,684).
The median of the mean age of blood units transfused per patient was 11 days in the freshest available blood group and 23 days in the oldest available blood group. In the primary analysis, post-transfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk of 0.94.
Interventions for renal vasculitis in adults
The Cochrane database of systematic reviews. 2020;1:Cd003232
BACKGROUND Renal vasculitis presents as rapidly progressive glomerulonephritis and comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions involve the use of steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This 2019 publication is an update of a review first published in 2008 and updated in 2015. OBJECTIVES To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to 21 November 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes. MAIN RESULTS Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I(2) = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I(2) = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I(2) = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I(2) = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I(2) = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I(2) = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab. AUTHORS' CONCLUSIONS Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
Effect of transfusion of washed red blood cells on serumpotassium level in hemodialysis patients
Turkish Journal of Medical Sciences. 2017;47((2)):407-411.
BACKGROUND/AIM: This study aimed to compare washed red blood cell (WRBC) transfusion versus nonwashed RBC (NWRBC) transfusion in terms of posttransfusion potassium levels in dialysis patients on a day when the patient did not receive dialysis. MATERIALS AND METHODS The patients were randomly assigned into two groups, i.e. those receiving WRBCs (n = 21) and those receiving NWRBCs (n = 17). Both groups received one unit of RBCs. Serum potassium and sodium levels were measured before and at the 1st, 2nd, 3rd, 4th, and 6th hours after transfusion. RESULTS In the WRBC group, the changes in the serum potassium levels at the 3rd, 4th, and 6th hours after transfusion were significant compared with pretransfusion levels. In the serum potassium levels mean decreases by 0.38 +/- 0.57 mEq/L at the 3rd hour (P = 0.006), by 0.32 +/- 0.47 mEq/L at the 4th hour (P = 0.005), and by 0.32 +/- 0.51 mEq/L at the 6th hour (P = 0.009) after transfusion were significant compared with the pretransfusion levels. CONCLUSION Although nonwashed RBC transfusion does not change serum potassium levels, washed RBC transfusion significantly reduces serum potassium levels. Washed RBC transfusion is considered to be safer in hemodialysis patients with hyperkalemia and anemia.
Epidemiology of RBC transfusions in patients with severe acute kidney injury: analysis from the Randomized Evaluation of Normal Versus Augmented Level Study
Critical Care Medicine. 2016;44((5)):892-900.
OBJECTIVE To assess the epidemiology and outcomes associated with RBC transfusion in patients with severe acute kidney injury requiring continuous renal replacement therapy. DESIGN Post hoc analysis of data from a multicenter, randomized, controlled trial. SETTING Thirty-five ICUs in Australia and New Zealand. PATIENTS Cohort of 1,465 patients enrolled in the Randomized Evaluation of Normal versus Augmented Level replacement therapy study. INTERVENTIONS Daily information on morning hemoglobin level and amount of RBC transfused were prospectively collected in the Randomized Evaluation of Normal versus Augmented Level study. We analyzed the epidemiology of such transfusions and their association with clinical outcomes. MEASUREMENTS AND MAIN RESULTS Overall, 977 patients(66.7%) received a total of 1,192 RBC units. By day 5, 785 of 977 transfused patients (80.4%) had received at least one RBC transfusion. Hemoglobin at randomization was lower in transfused than in nontransfused patients (94 vs 111g/L; p < 0.001). Mean daily hemoglobin was 88+/-7 and 99+/-12g/L in transfused and nontransfused patients. Among transfused patients, 228 (46.7%) had died by day 90 when compared with 426 (43.6%) of nontransfused patients (p = 0.27). Survivors received on average 316+/-261mL of RBC, whereas nonsurvivors received 302+/-362mL (p = 0.42). On multivariate Cox regression analysis, RBC transfusion was independently associated with lower 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79). However, we found no independent association between RBC transfusions and mortality when the analyses were restricted to patients surviving at least 5 days (hazard ratio, 1.29; 95% CI, 0.90-1.85). We found no independent association between RBC transfusion and renal replacement therapy-free days, mechanical ventilator-free days, or length of stay in ICU or hospital. CONCLUSIONS In patients with severe acute kidney injury treated with continuous renal replacement therapy, we found no association of RBC transfusion with 90-day mortality or other patient-centered outcomes. The optimal hemoglobin threshold for RBC transfusion in such patients needs to be determined in future randomized controlled trials.
Role of preoperative donor-specific transfusion and cyclosporine in haplo-identical living related renal transplant recipients
A prospective randomized trial of use of donor-specific transfusion and cyclosporine given 24 h before operation was performed in living related renal transplant recipients. The benefits, disadvantages and effect on graft and patient outcome was analyzed. Cyclosporine was started 72 h before operation and 48 h before donor-specific transfusion (DST). Fifteen patients received DST while another 15 age- and sex-matched living related renal allograft recipients on similar immunosuppression served as controls. Patient and donor demographics were similar in the two groups. The DST group had significantly fewer rejection episodes than the control group (0.26 vs. 1.1 rejection episode per patient, p < 0.01). There were fewer episodes of acute rejection in the first 3 months posttransplant in the DST group. Hyperresponder recipients (as tested by mixed lymphocyte cultures) also benefitted by DST which significantly reduced the number of acute rejection episodes (0.25 vs. 1 episode per hyperresponder patient, DST vs. control, p < 0.05). The need for dialysis, incidence of infections and other complications were similar in the two groups. Graft function at 3, 6, 9 and 12 months after transplant was significantly better in the DST group (p < 0.05). Graft survival at 1 year in DST group (85.5%) was not statistically different than control (74.8%). In conclusion, DST and cyclosporine given 24 h before live related renal transplantation is effective in improving graft function and reducing the number of acute rejection episodes which could have a beneficial effect on long-term graft survival.
Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial
Journal of Pediatrics. 1988;112((2):):284-90.
The results of a controlled trial to ascertain the usefulness of plasma infusion for the treatment of hemolytic-uremic syndrome (HUS) are reported. Criteria for admission were (1) observation within 8 days from first symptoms, (2) dialysis treatment required, and (3) no special treatments and no more than 25 ml blood/kg previously received. Children were subdivided according to age (less than or more than 3 years) and then randomly assigned to treatment with plasma or symptomatic therapy. Thirty-two children ranging in age from 4 months to 6 years entered this study; 17 received plasma (P+ group) and 15 only symptomatic therapy (P- group). The mean follow-up period was 16 months in both groups. Surgical renal biopsy was performed 29 to 49 days after onset in 11 P+ and 11 P- children, and 33 histologic findings were semiquantitatively evaluated. No death occurred in either group. No differences were found in blood pressure, proteinuria, or hematuria at the end of the follow-up period; in no case were severe arteriolar lesions found. There were no significant differences for the scores of the individual histologic measurements; on electron microscopy, no vascular changes were observed in seven children of the P+ group, whereas in five of seven of the P- group, thickening of the lamina rara interna and arteriolar damage were present. The ability of plasma to stimulate prostacyclin (PGI2) production, measured as its stable derivative 6-keto-PGF1 alpha, was within the normal range for all patients. In our patients with predominant glomerular involvement who were treated in a very early phase of HUS, infusions of plasma did not significantly influence the short- and medium-term clinical outcome and were not effective in severe HUS when given later in the course of the disease. A longer follow-up is needed to ascertain whether the presence of endothelial damage, demonstrated by electron microscopy in children who were not given plasma, is of clinical relevance.
Treatment of the childhood haemolytic uraemic syndrome with plasma. A multicentre randomized controlled trial. The French Society of Paediatric Nephrology
Pediatric Nephrology. 1988;2((3):):279-85.
Seventy-nine children with haemolytic uraemic syndrome (mean age 28 months) were randomly assigned either to a group receiving plasma infusions (plasma group, n = 39) or to a group treated conservatively (control group, n = 40). The duration of haemolysis, thrombocytopenia and anuria was similar in the two groups. Serum creatinine levels were similar in the two groups at the 1-month follow-up but were higher in the control group at 3 months (plasma group 49 +/- 14, control group 66 +/- 28 mumol/l; P less than 0.02) and at 6 months (plasma group 48 +/- 13, control group 63 +/- 21 mumol/l; P less than 0.005). The prevalence of proteinuria was also higher in the control group at the 6-month follow-up (plasma group 17%, control group 46%; P less than 0.02). However, differences were no longer significant after 1 year. Renal tissue was examined in 54 cases (plasma group, n = 27; control group, n = 27). Diffuse cortical necrosis was present in 7 cases in the control group but was absent in the plasma group (P less than 0.02). Taking into consideration the higher serum creatinine levels, the higher prevalence of proteinuria during the first 6 months of follow-up in the control group and the presence of diffuse cortical necrosis in this group compared with the plasma group, we conclude that plasma infusions should be regarded as beneficial. Further study is needed to determine which plasma fraction is involved.
A randomized study comparing leukocyte-depleted versus packed red cell transfusions in prospective cadaver renal allograft recipients
A prospective randomized study at a single renal transplant center between 1980 and 1982 compared the influence of leukocyte-depleted versus packed red cell pretransplantation blood transfusions on patient sensitization to leukocyte (HLA) antigens, likelihood of receiving a graft, and eventual transplantation results. All consenting potential cadaver renal transplant recipients (n = 107) were randomly assigned to receive transfusions at 6-week intervals with either packed red cells (Group 1) or leukocyte-poor red cells (Group 2) until they were transplanted. Actuarial graft and patient survival were identical for graft recipients in both groups. Although the likelihood of receiving a graft was associated with the level of pretransplant sensitization to leukocyte (HLA) antigens (p less than 0.02) as measured by the percent of panel reactive antibody (PRA), it was not associated with the type of blood used. The highest mean peak reactive PRA level for all patients showed a low but significant increase (29 +/- 4 versus 43 +/- 5%; p less than 0.0005) following entry into the transfusion protocol, but the rate of increase was the same for patients in both treatment groups. The likelihood of receiving a transplant was primarily associated with a history of prior graft rejection (p less than 0.05), and patients with prior graft loss had the greatest increase in sensitization following entry into the transfusion protocol. These findings indicate that using leukocyte-poor red cells for pretransplant transfusions provided no added benefit when compared with packed red cells in terms of patient sensitization, the likelihood of receiving a transplant, or eventual graft survival.
Peroperative blood-transfusion improve cadaveric renal-allograft survival in non-transfused recipients. A prospective controlled clinical trial
The effect of peroperative transfusion was studied in 27 patients who had never had a blood-transfusion or been pregnant and who were receiving their first cadaver renal allograft. 13 patients in the treatment group were given 2 units of whole stored blood at transplantation, whereas 14 patients in the control group were given no blood. Actuarial analysis after 2 years showed a graft survival of 85% at 1 year in the treated group compared with 34% at 1 year in the control group (p = 0.03). Transfusion of non-transfused patients during transplantation may be as effective as pregraft transfusion.