Reliability of serum creatinine-based formulae estimating renal function in non-critically ill surgery patients: Focus on augmented renal clearance.

WHAT IS KNOWN AND OBJECTIVES: Formulae estimating glomerular filtration rate (GFR) are frequently used to guide drug dosing. The objectives of this prospective single-center study were to evaluate agreement between these equations and measured creatinine clearance (CrCl) in non-critically ill surgery patients with normal kidney function and augmented renal clearance (ARC, CrCl ≥ 130 mL/min/1.73 m²), to determine predictors for disagreement, define a GFR estimator cut-off value identifying ARC and determine the ARC prevalence and duration in non-critically ill surgical patients. METHODS: Hospitalized adult non-critically ill abdominal and trauma surgery patients were eligible for inclusion. Measured CrCl based on an 8-hour urinary collection (CrCl8h ) was used as the primary method for determining kidney function. Agreement between equations and measured CrCl8h was assessed in terms of precision, defined as a bias within ±10 mL/min/1.73 m². Predictors for disagreement were identified for the most precise estimator using an ordinal logistic regression model with negative bias, agreement and positive bias as outcome variables. A receiver operating characteristic (ROC) analysis was performed to identify an estimator cut-off predicting ARC, which was subsequently applied for the daily proportion of patients displaying ARC and ARC duration. RESULTS AND DISCUSSION: During the study period (14/11/2013 - 13/05/2014), in 232 adult non-critically ill abdominal and trauma surgery patients, all estimators tend to underestimate CrCl8h (mean bias ranging from 17 to 22 mL/min/1.73 m²), especially in patients displaying ARC (mean bias ranging from 44 to 56 mL/min/1.73 m²). eGFRCKD-EPI performed the best. Younger age and low ASA score independently predicted underestimation of CrCl8h . Three different eGFRCKD-EPI cut-offs with decreasing sensitivity and increasing specificity (84, 95 and 112 mL/min/1.73 m²) identified, respectively, 65%, 44% and 14% patients displaying ARC. The median ARC duration was 4, 4 and 3 days, respectively. WHAT IS NEW AND CONCLUSION: In surgical patients, eGFR frequently underestimates measured CrCl, especially in young patients with low ASA score. eGFR cut-offs predicting ARC were identified.

Prevention of acute kidney injury and protection of renal function in the intensive care unit. Expert opinion of the Working Group for Nephrology, ESICM.

BACKGROUND: Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. OBJECTIVES: To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. METHOD: A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system. CONCLUSIONS AND RECOMMENDATIONS: Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest specific vasodilators [corrected] under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-009-1678-y) contains supplementary material, which is available to authorized users.

Long-term management of an implantable left ventricular assist device using low molecular weight heparin and antiplatelet therapy: a possible alternative to oral anticoagulants.

Between January 2004 and December 2005, out of 14 patients with decompensated heart failure who were treated with an INCOR left ventricular assist device (Berlin Heart AG, Berlin, Germany), 10 patients were kept on a long-term regime of low molecular weight heparin (LMWH) and antiplatelet therapy. The treatment objective was bridge-to-transplantation. All patients received LMWH in therapeutic doses according to body weight, in combination with daily aspirin 160 mg, clopidogrel 75 mg, and three times dipyridamole 75 mg. Effectiveness of the low molecular weight regime was monitored through measurement of antifactor Xa activity (base and peak levels). Antiplatelet therapy was monitored through weekly platelet function tests. Within this group of 10 patients, six patients successfully received transplants and four patients died, the latest death after 405 days of INCOR support. Causes of death were sepsis, intestinal hemorrhage, acute right ventricular failure, and one major stroke. Long-term management of INCOR assist devices using a combination of LMWH and antiplatelet therapy is feasible. This treatment strategy can serve as an alternative to oral anticoagulants.

Steroid-free immunosuppression during and after liver transplantation--a 3-yr follow-up report.

BACKGROUND/AIMS: Steroids are traditionally used in liver transplantation as a part of a triple or quadruple immunosuppressive regimen. Steroids act non-specifically and cause multiple side-effects. Most liver transplantation centers reduce the dosage of steroids and eventually withdraw them after various time intervals. A few steroid-free trials have been recently conducted after liver transplantation but long-term data are not yet available. In addition, in these trials steroids were usually given during surgery. We report the long-term (median = 40 months) follow-up data of a prospective pilot study designed to determine whether liver transplantation could be performed with no steroids at all (neither during nor after surgery). METHODS: Twenty-one consecutive liver transplantations in 20 adult patients between August 1998 and July 1999 were prospectively included in an ab initio steroid-free immunosuppressive protocol. Mean age was 54 yr (40-67 yr). Tacrolimus (through levels, 8-10 ng/mL) and azathioprine (1-2 mg/kg) were started after liver transplantation. Patients were not given steroids during or after liver transplantation except in the event of rejection or in case of tacrolimus or azathioprine toxicity requiring significant dose reduction and/or withdrawal. RESULTS: There has been no case of primary graft dysfunction or non-function. Eleven of 21 liver transplantations (52%) received no steroids throughout the whole study. Rejection developed in five of 21 liver transplantations (23.5%). These rejections responded to standard i.v. steroids (plus ATG in one patient), followed by an oral steroid taper stopped 3 months after rejection. Steroids were transiently given in six liver transplantations for non-immune reasons: two with tacrolimus-induced neurotoxicity, three cases where azathioprine was discontinued, and one for an allergic reaction; four of these six patients are off steroids at last follow-up. The 3-yr graft and patient survival is 95 and 100%, respectively. CONCLUSIONS: Steroids are not necessary in more than 50% of liver transplantations. Steroids were transiently needed to treat acute rejection in 23.5% liver transplantations and for toxicity of calcineurin inhibitors or azathioprine or other reason in 28%. Of the patients who received steroids, the majority (70%) was eventually taken off steroids. This prospective single-center pilot study shows that liver transplantation without steroids is feasible and yields no penalty in terms of acute and chronic rejection, immune graft loss, graft function, patient and graft survival.

Combined liver and (heart-)lung transplantation in liver transplant candidates with refractory portopulmonary hypertension.

BACKGROUND: Portopulmonary hypertension (PPHT) has a prevalence of 5-10% in liver transplantation (LiTx) candidates. Mild PPHT is reversible with LiTx, but more severe PPHT is a contraindication to LiTx given the high intraoperative mortality due to heart failure. Prostacyclin can reduce PPHT to a level at which LiTx can be performed. In patients refractory to that treatment, combined (heart-)lung-LiTx is the only life-saving option. METHODS: We report two cases of (heart-)lung-LiTx in patients with refractory severe PPHT. RESULTS: Patient 1, a 52-year-old female with viral cirrhosis and severe refractory PPHT, received a double-lung Tx followed by LiTx. After liver reperfusion, fatal heart failure occurred. Patient 2, a 42-year-old male with viral hepatitis and congenital liver fibrosis, also suffered from severe refractory PPHT. He successfully received an en bloc heart-lung Tx followed by LiTx. The rationale to replace the heart was an anticipated risk of intraoperative right heart failure after liver reperfusion and the technical ease of heart-lung versus double-lung Tx. CONCLUSION: Severe refractory PPHT is a fatal condition seen as a contraindication to LiTx. This condition can be treated by replacing thoracal organs in addition to the liver. Additional evidence via development of a registry is required to further support application of liver-(heart-)lung Tx in patients with severe refractory PPHT.