Atrial natriuretic peptide in the prevention of acute renal dysfunction after heart transplantation-a randomized placebo-controlled double-blind trial.

BACKGROUND: Acute kidney injury (AKI) and renal dysfunction after heart transplantation are common and serious complications. Atrial natriuretic peptide (ANP) has been shown to increase glomerular filtration rate (GFR) and exert renoprotective effects when used for the prevention/treatment of AKI in cardiac surgery. We tested the hypothesis that intraoperative and postoperative administration of ANP could prevent a postoperative decrease in renal function early after heart transplantation. METHODS: Seventy patients were randomized to receive either ANP (50 ng/kg/min) (n = 33) or placebo (n = 37) starting after induction of anesthesia and continued for 4 days after heart transplantation or until treatment with dialysis was started. The primary end-point of the present study was measured GFR (mGFR) at day 4, assessed by plasma clearance of a renal filtration marker. Also, the incidence of postoperative AKI and dialysis were assessed. RESULTS: Median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) ml/min/1.72 m2 for the placebo and ANP groups, respectively (p = .705). During ongoing ANP infusion, the need for dialysis was 21.6% and 9.1% for the placebo and ANP groups, respectively (p = .197). The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p = .616). The incidences of AKI stage 1 were 32.4% and 21.2% for the placebo and ANP groups, respectively (p = .420) and for AKI stage 2 or 3, 37.8% and 42.4%, respectively (p = .808). CONCLUSION: The study failed to detect that ANP infusion attenuates renal dysfunction or decreases the incidence of AKI after heart transplantation.

Dextran-based priming solution during cardiopulmonary bypass attenuates renal tubular injury-A secondary analysis of randomized controlled trial in adult cardiac surgery patients.

BACKGROUND: Acute kidney injury (AKI) is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In the present secondary analysis of a blinded randomized controlled trial, we evaluated the effects of a colloid-based versus a conventional crystalloid-based prime on tubular injury and postoperative renal function in patients undergoing cardiac surgery with CPB. METHODS: Eighty-four adult patients undergoing cardiac surgery with CPB were randomized to receive either a crystalloid- or colloid- (dextran 40) based CPB priming solution. The crystalloid solution was based on Ringer-Acetate plus mannitol. The tubular injury biomarker, N-acetyl-b-D-glucosaminidase (NAG), serum creatinine and diuresis were measured before, during and after CPB. The incidence of AKI was assessed according to the KDIGO criteria. RESULTS: The urinary-NAG/urinary-creatinine ratio rose in both groups during and after CPB, with a more pronounced increase in the crystalloid group (p = .038). One hour after CPB, the urinary-NAG/urinary-creatinine ratio was 88% higher in the crystalloid group (4.7 ± 6.3 vs. 2.5 ± 2.7, p = .045). Patients that received the dextran 40-based priming solution had a significantly lower intraoperative diuresis (p < .001) compared to the crystalloid group. The incidence of AKI was 18% in the colloid and 22% in the crystalloid group (p = .66). Postoperative serum creatinine did not differ between groups. CONCLUSIONS: In patients undergoing cardiac surgery with CPB, colloid-based priming solution (dextran 40) induced less renal tubular injury compared to a crystalloid-based priming solution. Whether a colloid-based priming solution will improve renal outcome in high-risk cardiac surgery, or not, needs to be evaluated in future studies on higher risk cardiac surgery patients.

Serum biomarkers of brain injury after uncomplicated cardiac surgery: Secondary analysis from a randomized trial.

BACKGROUND: Postoperative cognitive dysfunction is common after cardiac surgery. Postoperative measurements of brain injury biomarkers may identify brain damage and predict cognitive dysfunction. We describe the release patterns of five brain injury markers in serum and plasma after uncomplicated cardiac surgery. METHODS: Sixty-one elective cardiac surgery patients were randomized to undergo surgery with either a dextran-based prime or a crystalloid prime. Blood samples were taken immediately before surgery, and 2 and 24 h after surgery. Concentrations of the brain injury biomarkers S100B, glial fibrillary acidic protein (GFAP), tau, neurofilament light (NfL) and neuron-specific enolase (NSE)) and the blood-brain barrier injury marker ß-trace protein were analyzed. Concentrations of brain injury biomarkers were correlated to patients' age, operation time, and degree of hemolysis. RESULTS: No significant difference in brain injury biomarkers was observed between the prime groups. All brain injury biomarkers increased significantly after surgery (tau +456% (25th-75th percentile 327%-702%), NfL +57% (28%-87%), S100B +1145% (783%-2158%), GFAP +17% (-3%-43%), NSE +168% (106%-228%), while ß-trace protein was reduced (-11% (-17-3%). Tau, S100B, and NSE peaked at 2h, NfL and GFAP at 24 h. Postoperative concentrations of brain injury markers correlated to age, operation time, and/or hemolysis. CONCLUSION: Uncomplicated cardiac surgery with cardiopulmonary bypass is associated with an increase in serum/plasma levels of all the studied injury markers, without signs of blood-brain barrier injury. The biomarkers differ markedly in their levels of release and time course. Further investigations are required to study associations between perioperative release of biomarkers, postoperative cognitive function and clinical outcome.

Atrial natriuretic peptide does not degrade the endothelial glycocalyx: A secondary analysis of a randomized porcine model.

BACKGROUND: The atrial natriuretic peptide (ANP) released from the heart regulates intravascular volume and is suspected to increase capillary permeability. Contradictory results regarding ANP and glycocalyx degradation have been reported. The aim of this study was to investigate if an infusion of ANP causes degradation of the endothelial glycocalyx. METHODS: Twenty pigs, pretreated with 250 mg methylprednisolone, were randomized to receive an infusion of either ANP (50 ng/kg/min) (n = 10) or 0.9% NaCl (n = 10) during 60 min. Endothelial glycocalyx components (heparan sulphate proteoglycan and hyaluronic acid), Hct, calculated plasma volume and colloid osmotic pressure were measured from baseline to 60 min. RESULTS: There was no difference between the control and intervention groups for heparan sulphate proteoglycan and hyaluronic acid corrected for the change in plasma volume (P = .333 and 0.197). Hct increased with 1.8 ± 2.2% in the intervention group (P = .029) with no change -0.5 ± 2.3% in the control group (P = .504). The plasma volume decreased in the intervention group with -8.4 ± 10% (P = .034) with no change in the control group 3.1 ± 12% (P = .427). Median changes in colloid osmotic pressures in the control and intervention group were -0.39 [95% CI, -1.88-0.13] and 0.9 [95% CI, 0.00-1.58], respectively (P = .012). CONCLUSIONS: In this randomized porcine study, an ANP infusion did not cause endothelial glycocalyx degradation but decreased the plasma volume most probably due to precapillary vasodilation and increased filtration.

Measured and not estimated glomerular filtration rate should be used to assess renal function in heart transplant recipients.

BACKGROUND: In organ transplanted patients, impaired renal function is of major prognostic importance and influences therapeutic decisions. Therefore, monitoring of renal function with glomerular filtration rate (GFR) is of importance, both before and after heart transplantation (HTx). The GFR can be measured directly (mGFR) or estimated (eGFR) with equations based on circulating creatinine or cystatin C levels. However, these equations have not been thoroughly validated in the HTx population. METHODS: We investigated the correlation, agreement and accuracy between mGFR (using (51)Cr-ethylenediaminetetraacetic acid or iohexol clearance) and three commonly used eGFR equations (Modification of Diet in Renal Disease, Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration) in a retrospective analysis of 416 HTx recipients followed between 1988 and 2012. Comparisons were performed prior to transplantation and at 1, 5 and 10 years of follow-up. RESULTS: The correlations between eGFR and mGFR were only moderate, with r-values ranging from 0.55 preoperatively to 0.82 during follow-up. Most importantly, the level of agreement between eGFR and mGFR was very low for all three estimates, with percentage errors ranging from 93.3 to 157.3%. Also, the percentage of patients with eGFR within 30% of mGFR (P30) rarely reached the National Kidney Foundation recommended minimum level of 75%. CONCLUSION: We argue that the accuracy and the precision of the most commonly used estimation equations for assessment of kidney function are unacceptably low and we believe that mGFR should be used liberally as the basis for clinical decision-making both before and after HTx when eGFR is subnormal.

Hemostatic effects of a dextran-based priming solution for cardiopulmonary bypass: A secondary analysis of a randomized clinical trial.

INTRODUCTION: Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solutions, one colloid-based (dextran 40) and one crystalloid-based. MATERIALS AND METHODS: Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelastometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion requirements were recorded. RESULTS: Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot formation time (+41 ± 21 % vs. +8 ± 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (-37 ± 12 % vs. -7 ± 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (-14 ± 29 % vs. -1 ± 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed. CONCLUSIONS: Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on hemostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.

The trajectory of renal function following mechanical circulatory support and subsequent heart transplantation.

AIM: Patients with advanced heart failure (HF) frequently suffer from renal insufficiency. The impact of durable mechanical circulatory support (MCS) and subsequent heart transplantation (HTx) on kidney function is not well described. METHODS AND RESULTS: We studied patients with advanced HF who received durable MCS as bridge to transplantation (BTT) and underwent subsequent HTx at our centre between 1996 and 2018. Glomerular filtration rate (GFR) was measured by 51 Cr-EDTA or iohexol clearance during heart failure work-up; 3-6 months after MCS; and 1 year after HTx. Chronic kidney disease (CKD) was classified according to KDIGO criteria based on estimated GFR. A total of 88 patients (46 ± 15 years, 84% male) were included, 63% with non-ischaemic heart disease. The median duration of MCS-treatment was 172 (IQR 116-311) days, and 81 subjects were alive 1 year after HTx. Measured GFR increased from 54 ± 19 during HF work-up to 60 ± 16 mL/min/1.73 m2 after MCS (P < 0.001) and displayed a slight but nonsignificant decrease to 57 ± 22 mL/min/1.73 m2 1 year after HTx (P = 0.38). The trajectory of measured GFR did not differ between pulsatile and continuous flow (CF) pumps. Among patients 35-49 years and those who were treated in the most recent era (2012-2018), measured GFR increased following MCS implantation and subsequent HTx. Estimated GFR displayed a similar course as did measured GFR. CONCLUSIONS: In patients with advanced heart failure, measured GFR improved after MCS with no difference between pulsatile and CF-pumps. The total study group showed no further increase in GFR following HTx, but in certain subgroups, including patients aged 35-54 years and those treated during the latest era (2012-2018), renal function appeared to improve after transplant.

Dextran- Versus Crystalloid-Based Prime in Cardiac Surgery: A Prospective Randomized Pilot Study.

BACKGROUND: The optimum priming fluid for the cardiopulmonary bypass (CPB) circuit is still debated. We compared a new hyperoncotic priming solution containing dextran 40, which has an electrolyte composition that mimics extracellular fluid, with a standard crystalloid-based prime. METHODS: Eighty cardiac surgery patients were included in this double-blind, randomized, single-center study. Patients were randomized to either a dextran-based prime or a crystalloid prime containing Ringer's acetate and mannitol. The primary end point was colloid oncotic pressure in serum during CPB. Secondary end points included fluid balance, bleeding and transfusion requirements, pulmonary function, hemolysis, systemic inflammation, and markers of renal, hepatic, myocardial, and brain injury. Blood samples were collected before, during, and after CPB. RESULTS: Colloid oncotic pressure was higher in the dextran group than in the crystalloid prime group during CPB (18.8 ± 2.9 versus 16.4 ± 2.9 mm Hg; P < .001) and 10 minutes after CPB (19.2 ± 2.7 versus 16.8 ± 2.9 mm Hg; P < .001). Patients in the dextran group required less intravenous fluid during CPB (1090 ± 499 versus 1437 ± 543 mL; P = .004) and net fluid balance was less positive 12 hours after surgery (1431 ± 741 versus 1901 ± 922 mL; P = .014). Plasma-free hemoglobin was significantly lower in the dextran group 2 hours after CPB (0.18 ± 0.11 versus 0.41 ± 0.33; P = .001). There were no significant differences in bleeding, transfusion requirements, organ function, systemic inflammation, or brain and myocardial injury markers between groups at any time point. CONCLUSIONS: Our results suggest that a hyperoncotic dextran-based priming solution preserves intraoperative colloid oncotic pressure compared with crystalloid prime. Larger studies with clinically valid end points are necessary to evaluate hyperoncotic prime solutions further.

Effects of atrial natriuretic peptide on renal function during cardiopulmonary bypass: a randomized pig model.

OBJECTIVES: Acute kidney injury is a well-known complication after cardiac surgery and cardiopulmonary bypass (CPB). In this experimental animal study, we evaluated the effects of atrial natriuretic peptide (ANP) on renal function, perfusion, oxygenation and tubular injury during CPB. METHODS: Twenty pigs were blindly randomized to continuous infusion of either ANP (50 ng/kg/min) or placebo before, during and after CPB. Renal blood flow as well as cortical and medullary perfusion was measured. Blood was repeatedly sampled from the renal vein. Glomerular filtration rate was measured by infusion clearance of 51Cr-EDTA. RESULTS: Glomerular filtration rate was higher (P < 0.001), whereas renal blood flow or renal oxygen delivery was not affected by ANP during CPB. Renal oxygen consumption did not differ between groups during CPB, whereas renal oxygen extraction was higher in the ANP group (P = 0.03). Urine flow and sodium excretion were higher in the ANP group during CPB. Blood flow in the renal medulla, but not in the cortex, dropped during CPB, an effect that was not seen in the animals that received ANP. CONCLUSIONS: ANP improved renal function during CPB. Despite impaired renal oxygenation, ANP did not cause tubular injury, suggesting a renoprotective effect of ANP during CPB. Also, CPB induced a selectively reduced blood flow in the renal medulla, an effect that was counteracted by ANP.

Renal function and outcome after heart transplantation.

OBJECTIVES: To investigate whether measured glomerular filtration rate (mGFR) is a risk factor for death and/or end-stage renal disease (ESRD) after heart transplantation (HTx). METHODS: All adult patients (n = 416) who underwent HTx between 1988 and 2010 were included. mGFR was performed both preoperatively and postoperatively as annual follow-up. Eight patients received a concomitant kidney transplant (KTx), and 15 underwent late KTx due to chronic renal failure after HTx. RESULTS: The mean drop in mGFR compared with the preoperative value was 12% during the first year after HTx. Preoperative mGFR was not predictive of mortality or ESRD. Older or the use of a ventricular assist device (VAD) were preoperative predictors of death. Long-term survival was significantly worse in the patients who experienced a >25% decrease in mGFR during the first year after transplantation. The need for acute postoperative renal replacement therapy (RRT) was associated with impaired survival but did not predict ESRD among survivors. On multivariable analyses, previous heart surgery, preoperative VAD, and a lower mGFR were all predictors of RRT. In the most recent period, death without previous ESRD was lower, and the only preoperative factors associated with ESRD by multivariable analyses were mechanical ventilation and diabetes mellitus. CONCLUSIONS: Pretransplantation mGFR was not predictive of mortality or ESRD after HTx, but necessitated simultaneous or late-stage KTx in this selected population of patients. However, patients with a decrease in >25% mGFR during the first year post-transplantation, as well as early postoperative dialysis-dependent acute renal dysfunction, had a poor prognosis. We suggest that patients with severely impaired kidney function, irrespective of pretransplantation renal function, still should be considered for HTx, but also encourage careful interpretation of our results given the selection bias involved in this population.

Endothelial cell antibody-mediated rejection and successful retransplantation in a heart transplanted patient.

Antibody-mediated rejection (AMR) plays a significant role in cardiac allograft dysfunction, and recently a consensus regarding the diagnosis of AMR has been published. To our knowledge, it has not previously been reported that acute graft failure related to AMR, and antiendothelial cell antibodies can successfully be diagnosed to allow the patient to receive the outlined treatment and undergo a subsequent retransplantation.

Percutaneous coronary intervention facilitated by extracorporeal membrane oxygenation support in a patient with cardiogenic shock.

A 60-year-old man was admitted to our department with non ST-segment elevation myocardial infarction complicated by cardiogenic shock. Total revascularization, using percutaneous coronary intervention facilitated by extracorporeal membrane oxygenation support, was performed, with a favorable outcome.