Association of Acute Kidney Injury Receiving Kidney Replacement Therapy With Prognosis of Critically Ill Patients With and Without Cancer: A Retrospective Study.

OBJECTIVES: To assess outcomes of cancer patients receiving kidney replacement therapy due to acute kidney injury in ICUs and compare these with other patient groups receiving kidney replacement therapy in ICUs. DESIGN: Retrospective registry analysis. SETTING: Prospectively collected database of 296,424 ICU patients. PATIENTS: Patients with and without solid cancer with acute kidney injury necessitating kidney replacement therapy were identified and compared with those without acute kidney injury necessitating kidney replacement therapy. INTERVENTIONS: Descriptive statistics were used to ascertain prevalence of acute kidney injury necessitating kidney replacement therapy and solid cancer in ICU patients. Association of acute kidney injury necessitating kidney replacement therapy and cancer with prognosis was assessed using logistic regression analysis. To compare the attributable mortality of acute kidney injury necessitating kidney replacement therapy, 20,154 noncancer patients and 2,411 cancer patients without acute kidney injury necessitating kidney replacement therapy were matched with 12,827 noncancer patients and 1,079 cancer patients with acute kidney injury necessitating kidney replacement therapy. MEASUREMENTS AND MAIN RESULTS: Thirty-five thousand three hundred fifty-six ICU patients (11.9%) had solid cancer. Acute kidney injury necessitating kidney replacement therapy was present in 1,408 (4.0%) cancer patients and 13,637 (5.2%) noncancer patients. Crude ICU and hospital mortality was higher in the cancer group (646 [45.9%] vs 4,674 [34.3%], p < 0.001, and 787 [55.9%] vs 5,935 [43.5%], p < 0.001). In multivariable logistic regression analyses, odds ratio (95% CI) for hospital mortality was 1.73 (1.62-1.85) for cancer compared with no cancer 3.57 (3.32-3.83) for acute kidney injury necessitating kidney replacement therapy and 1.07 (0.86-1.33) for their interaction. In the matched subcohort, attributable hospital mortality of acute kidney injury necessitating kidney replacement therapy was 56.7% in noncancer patients and 48.0% in cancer patients. CONCLUSIONS: Occurrence rate of acute kidney injury necessitating kidney replacement therapy and prognosis in ICU patients with solid cancer are comparable with other ICU patient groups. In cancer, acute kidney injury necessitating kidney replacement therapy is associated with higher crude hospital mortality. However, the specific attributable mortality conveyed by acute kidney injury necessitating kidney replacement therapy is actually lower in cancer patients than in noncancer patients. Diagnosis of cancer per se does not justify withholding kidney replacement therapy.

Association of Body Mass Index and Outcome in Acutely Ill Patients With Chronic Kidney Disease Requiring Intensive Care Therapy.

OBJECTIVE: An association of body mass index (BMI) and outcome, the "obesity paradox," has been described in patients with chronic kidney disease (CKD) and end-stage renal disease. We sought to assess whether a potential beneficial effect of a high body mass is also seen in CKD patients with critical illness. METHODS: In a retrospective analysis of a prospectively collected database of 123,416 patients from 107 Austrian intensive care units (ICUs) in whom BMI was available, the association of 6 groups of BMI and hospital mortality was assessed in 12,206 patients with CKD 3-5 by univariate and multivariate logistic regression analyses. RESULTS: Patients with CKD were sicker, had a longer ICU stay, and had a higher ICU and hospital mortality than those without. The association of BMI and outcome in CKD patients indicated a U-shaped curve with the highest mortality in patients with BMI <20 and ≥40, and the lowest with a BMI between ≥25 and <40. This relationship was also significant in a multivariate analysis adjusted for severity of illness assessed by Simplified Acute Physiology Score III score, age, gender, admission diagnosis, and pre-existing comorbidities. It was not found in patients with CKD 5 on renal replacement therapy, in patients below 60 years of age, and those with diabetes mellitus requiring insulin treatment. CONCLUSIONS: BMI is associated with better outcomes in CKD 3-5 patients who have acquired acute intermittent diseases and are admitted to an ICU, but not those requiring renal replacement therapy. This higher tolerance to acute disease processes may in part explain the "obesity paradox" observed in CKD patients.

Very early changes in serum creatinine are associated with 30-day mortality after cardiac surgery: A cohort study.

BACKGROUND: Acute kidney injury predicts adverse outcomes after cardiac surgery. OBJECTIVES: To determine whether ultra-short-term changes (within 120 min) in serum creatinine (SCrea) levels after cardiac surgery predict clinical outcomes (30-day mortality). DESIGN: Observational cohort study. SETTING: Austrian tertiary referral centre. PATIENTS: A total of 7651 patients scheduled to undergo elective cardiac surgery. MAIN OUTCOME MEASURES: We analysed SCrea levels measured pre-operatively (baseline) and within 120 min after surgery. We also adjusted the postoperative SCrea levels for fluid balance. Patients were grouped according to the difference between the pre and postoperative SCrea levels (ΔSCreaAdmICU). We performed univariable and multivariable analyses to determine the association between changes in SCrea levels and 30-day mortality. RESULTS: After cardiac surgery, the SCrea level decreased in 5923 patients and increased in 1728 patients. Increased SCrea levels were associated with a 21% increase in 30-day mortality. Even minimal increases in SCrea (0 to <26.5 µmol l) were significantly associated with 30-day mortality [hazard ratio (HR), 1.98; 95% confidence interval (CI), 1.54 to 2.55; P < 0.001]. Adjustments for fluid balance strengthened the above association (increases of 0 to <26.5 µmol l: HR, 1.78; 95% CI, 1.40 to 2.26; P < 0.001; increases of at least 26.5 µmol l: HR, 2.40; 95% CI, 1.68 to 3.42; P < 0.001). CONCLUSION: Even minimal, ultra-short-term increases in SCrea levels after cardiac surgery are associated with increased 30-day mortality. Adjustment for fluid balance strengthens this association. The change in SCrea between baseline and after admission to the Intensive Care Unit (ΔSCreaAdmICU) can serve as a simple, cheap and widely available marker for very early risk stratification after cardiac surgery.

An acetate-buffered balanced crystalloid versus 0.9% saline in patients with end-stage renal disease undergoing cadaveric renal transplantation: a prospective randomized controlled trial.

BACKGROUND: Recent studies have shown a decline in glomerular filtration rate and increased renal vasoconstriction after administration of normal saline when compared with IV solutions with less chloride. In this study, we investigated the impact of normal saline versus a chloride-reduced, acetate-buffered crystalloid on the incidence of hyperkalemia during cadaveric renal transplantation. The incidence of metabolic acidosis and kidney function were secondary aims. METHODS: In this prospective randomized controlled trial, 150 patients received normal saline or an acetate-buffered balanced crystalloid during and after cadaveric renal transplantation. Venous blood gases were obtained at the start of anesthesia and every 30 minutes until discharge from the postoperative surveillance unit. Serum creatinine and 24-hour urine output were obtained on postoperative days 1, 3, and 7. RESULTS: Patients received a similar amount of fluid (median: 2625mL [interquartile range: 2000 to 3100] vs 2500 mL [2000 to 3050], P = 0.83). Hyperkalemia, defined as serum potassium >5.9 mmol/L, occurred in 13 patients (17%) in the saline and 15 (21%) in the balanced group (P = 0.56; difference between proportions -0.037 [-16.5% to 8.9%]). Minimum base excess was lower in the saline group compared with the balanced regimen (-4.5 mmol/L [-6 to -2.4] vs -2.6 mmol/L [-4 to -1], P < 0.001) and maximum chloride was significantly higher in the saline group (109 mmol/L [107 to 111] vs 107 mmol/L [105 to 109], P < 0.001). No difference in creatinine or urine output was seen postoperatively. Significantly more patients needed catecholamines in the saline group (30% vs 15%, P = 0.03). CONCLUSIONS: The incidence of hyperkalemia differed by less than 17% between groups. Use of balanced crystalloid resulted in less hyperchloremia and metabolic acidosis. Significantly more patients in the saline group required administration of catecholamines for circulatory support.

NephroCheck data compared to serum creatinine in various clinical settings.

BACKGROUND: Acute kidney injury is frequently observed at the intensive care unit, after surgery, and after toxic drug administration. A rise in serum creatinine and a fall in urine output are consequences of much earlier injury to the most sensitive part of tubular cells located at the proximal tubule. The aim of the present study was to investigate the course of two cell-cycle arrest urinary biomarkers compared to serum creatinine in four clinical settings: ischemic reperfusion injury, cardiac failure, severe acute kidney injury, and chemotherapy-induced kidney injury. METHODS: A recently developed bedside test known as NephroCheck measures two urinary parameters: insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2). The test is based on a sandwich immunoassay technique. The final test output, labeled AKIRisk, is shown as a numeric result. RESULTS: This report revealed that [IGFBP7] · [TIMP-2] in urine rise rapidly prior to any change in serum creatinine. A unique feature of all four clinical settings is that a rapid decline predicts the recovery of kidney function. Besides, a subclinical kidney injury might be detected by the test. CONCLUSION: This bedside test detects biomarkers of renal injury. A rapid decline in AKIRisk was associated with the restoration of kidney function, whereas a prolonged high AKIRisk score was associated with end-stage renal disease. However, the dynamics seem to differ, depending on the cause and the extent of injury. Further studies will be needed to clarify the issue.

Systemic consequences of acute kidney injury.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is a frequent and serious event associated with a high rate of complications, with an increased risk of progression to multiple organ dysfunction and excessive 'attributable' mortality. AKI affects all physiologic functions and organ systems with interrelated mechanisms, including the 'classical' consequences of the uremic state, the inflammatory nature of AKI per se and resulting systemic effects, the modulating effect of AKI in the presence of an (inflammatory) underlying disease process and the multiple untoward effects induced by renal replacement therapy (RRT) and anticoagulation. RECENT FINDINGS: A rapidly increasing body of evidence is clarifying these systemic effects that are the reflection of a broad common pathology that ultimately results in an 'augmented' inflammation and impairment of immunocompetence. This includes the release of cytokines and inflammatory mediators, increase in oxidative stress, activation of various immune cells, neutrophil extravasation, generalized endothelial injury, increased vascular permeability and tissue oedema formation. SUMMARY: These systemic phenomena associated with AKI induce distant organ injury affecting all organ systems with clinically the most relevant effects being exerted on the lungs, the intestines and liver and the heart and predispose the progression to multiple organ dysfunction syndrome and death. Currently available renal replacement therapy modalities are incapable of compensating for these systemic consequences of AKI.

Fibrinogen reduction and bleeding complications in plasma exchange, immunoadsorption and a combination of the two.

BACKGROUND: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. METHODS: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). RESULTS: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. CONCLUSION: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.

[Long-term consequences after intensive therapy]. / Langzeitfolgen nach Intensivtherapie.

Many intensive care patients are affected by serious persistent or new physical, cognitive, psychological, and social consequences after discharge (post-ICU syndrome). This has an impact on the rest of life as well as the prognosis. To reduce or avoid these complications and structured treatment after discharge must be essential goals of intensive care medicine. Prevention of PICS is of central importance. The knowledge that many elements of the symptoms are triggered or intensified by therapeutic treatments as part of intensive therapy offers the opportunity to modify. Therapy must be designed to reduce potential sequelae, with the avoidance of overtreatment, such as sedation. These understanding must lead to critically questioning who is admitted to an intensive care unit and for whom a realistic therapy goal in terms of functionality, quality of life and life expectancy can be achieved. Ultimately, the treatment of intensive care patients must not end when they are discharged from the intensive care unit or hospital. Patients at risk for the very different facets of a PICS must be identified and linked to appropriate care institutions. This requires the establishment of post-ICU facilities, such as consultation hours in clinics or outpatient clinics.

Single-dose application of antithrombin as a potential alternative anticoagulant during continuous renal replacement therapy in critically ill patients with advanced liver cirrhosis: a retrospective data analysis.

BACKGROUND: Adequate anticoagulation is essential to achieve efficient and cost-effective continuous renal replacement therapy (CRRT). However, in critically ill patients with advanced liver cirrhosis, this goal is challenging because of the concomitant bleeding disorder. Therefore, the evaluation of alternative anticoagulants is necessary. METHODS: In this retrospective study, we analyzed data of 37 CRRTs in 16 critically ill patients with advanced liver cirrhosis and acute kidney injury admitted to a medical intensive care unit between 2006 and 2008 and included patients undergoing CRRT with either single doses of antithrombin (AT) or continuous low-dose heparin as a sole anticoagulant. The primary outcome measure was lifetime of single CRRT filters. RESULTS: Data were available for 13 CRRT filters for patients anticoagulated with single doses of AT (n = 6), and 24 CRRT filters for patients anticoagulated continuously with low-dose heparin (n = 10). Means of single-filter lifetimes were significantly higher in the AT group compared with the heparin group (45 ± 29 hours [95% confidence interval 27-62 hours] vs 26 ± 23 hours [95% confidence interval 16-36 hours]; P = 0.03), whereas mean filter lifetimes of individual patients were comparable (median [25th-75th percentile] 30 hours [21-59 hours] vs 28 hours [17-70 hours]; P = 0.79). CONCLUSIONS: Our data suggest that anticoagulation with single doses of AT may be an alternative to continuously administered low-dose heparin in critically ill patients with advanced liver cirrhosis during CRRT. However, additional controlled trials are necessary to confirm our findings.

Early basal insulin therapy decreases new-onset diabetes after renal transplantation.

No effective interventions to reduce risk for new-onset diabetes after transplantation (NODAT), a condition associated with postoperative hyperglycemia and reduced patient and graft survival, have been established. In this 1-year, proof-of-concept clinical trial, we randomly assigned 50 renal transplant recipients to immediate-postoperative isophane insulin for evening blood glucose ≥140 mg/dl (treatment group) or short-acting insulin and/or oral antidiabetic agents for blood glucose ≥180-250 mg/dl (standard-of-care control group). We included only patients without a history of diabetes who received tacrolimus. By the third postoperative evening, all patients in the treatment group had blood glucose ≥140 mg/dl and were subsequently treated with basal insulin; during the first 3 weeks after transplantation, the mean ± SD daily insulin dosage was 17±11 IU/d. Among controls, 23 (92%) of 25 had blood glucose ≥200 mg/dl and 18 (72%) of 25 received standard-of-care antihyperglycemic treatment. Asymptomatic hypoglycemia occurred five times in the treatment group and once in the control group. Throughout follow-up, the treatment group had 73% lower odds of NODAT (odds ratio, 0.27) than the control group, and hemoglobin A1c was on average 0.38% lower in the treatment group than the control group. Twelve months after transplantation, all patients in the treatment group were insulin-independent, whereas 7 (28%) of 25 controls required antidiabetic agents. The groups did not differ for insulin sensitivity, but the treatment group showed better ß-cell function throughout the 1-year follow-up. In conclusion, this study suggests regimens that include basal insulin significantly reduce the odds for NODAT after renal transplantation, presumably via insulin-mediated protection of ß cells.

Plasma amino acid imbalance: dangerous in chronic diseases?

PURPOSE OF REVIEW: In various diseases amino acid imbalances occur which have been described especially in the 1980s of the last century. It was noted that some of these imbalances may exert specific negative physiological effects. However, mainly because of economic reasons, no real attempts have been made to develop special amino acid solutions for disease processed associated with amino acid imbalances to restore normal amino acid concentrations. RECENT FINDINGS: A recent study performed in the fruit-fly Drosophila indicated that modifying the amino acid supply may influence both lifespan and fecundity. It was shown that adding amino acids but not carbohydrates or fat to a restricted diet decreases lifespan. In contrast, administration of certain amino acids especially of methionine increased fecundity without decreasing lifespan. It is known that dietary restriction can decrease fecundity at the cost of a prolonged lifespan. SUMMARY: Recent investigations revealed that amino acids are powerful molecules in mediating cell signalling. Therefore, it can be hypothesized that the severe amino acid imbalances as observed in uraemia or liver failure may exert a relevant impact on various physiologic processes and on organ function. The recent results described in Drosophila should stimulate a new research area on the effect of amino acid supply in various disease processes.

[Acute renale failure in burns - causes, consequences and avoidance strategies]. / Akutes Nierenversagen bei Brandverletzten - Ursachen, Konsequenzen und Vermeidungstrategien.

Acute renal failure (ARF) is a common and dangerous complication in intensive care medicine. Especially critical ill patients, who are suffering from major burns, have a high risk to develop ARF as a consequence of their trauma. Many factors, including the trauma itself, the damage of soft tissue and consecutive rhabdomyolysis, the development of the burn illness and therapeutic interventions play also a major role in this context. These circumstances have a major impact on the morbidity and mortality of severely burned patients. The aim of this manuscript is to review the reasons for the development of an ARF in burn patients as well as its consequences; moreover it highlights potential strategies to avoid ARF in critically ill burned patients.

Tonicity balance in patients with hypernatremia acquired in the intensive care unit.

BACKGROUND: Hypernatremia is a serious electrolyte disturbance and an independent risk factor for mortality in critically ill patients. In many cases, hypernatremia is an iatrogenic problem that develops in the intensive care unit (ICU). STUDY DESIGN: Case series. SETTING & PARTICIPANTS: 45 patients were studied in a medical ICU. For inclusion in the study, patients needed to show an increase in serum sodium concentration to greater than 149 mEq/L from an initial concentration of less than 146 mEq/L. OUTCOMES: Solute balance, fluid balance, and both. Causes of hypernatremia. MEASUREMENTS: The daily mass balance of sodium, potassium, and water over 1- to 3-day intervals was measured while serum sodium levels were increasing. RESULTS: During the study period, 69 of 981 patients (7%) acquired hypernatremia after admission to the ICU. Of these, 45 had sufficient data for evaluation. Maximum serum sodium levels were 150 to 164 mEq/L. The average duration of hypernatremia was 2 days (range, 1 to 10 days), with an average onset on day 5.9 +/- 4.3 of the ICU stay. Patients were classified as having a positive solute balance (n = 17; 38%), negative fluid balance (n = 20; 44%), or both (n = 8; 18%). The most important extrarenal factors contributing to hypernatremia were fever (45%) and diarrhea (18%). Polyuria was observed in 38% of patients and 35% had acute renal failure. Hypertonic solutions were administered to 27% of patients. LIMITATIONS: Retrospective analysis; lack of daily measurement of body weight. CONCLUSION: ICU-acquired hypernatremia is associated with multiple factors associated with negative fluid and positive solute balance.

Prognosis in patients with congestive heart failure and subacute renal failure treated with hemodialysis.

BACKGROUND: Renal dysfunction confers a grave prognosis for patients with congestive heart failure (CHF); even small increases in plasma creatinine are associated with excess mortality. Little, however, is known about prognostic indices and outcome in patients with CHF who (sub-)acutely progress to dialysis dependency. DESIGN AND SETTING: We evaluated prognostic indices in a retrospective cohort analysis of non-critically ill patients with CHF who (sub-)acutely progressed to dialysis-dependent renal failure. PATIENTS AND METHODS: 46 patients (95% ischemic cardiomyopathy) with CHF (NYHA III-IV) with dialysis-dependent renal failure (acute and acute-to-chronic renal failure) were analyzed. Demographic factors and patient characteristics, of cardiac function parameters and renal parameters were recorded longitudinally. MAIN RESULTS: CHF patients progressing to dialysis- dependent renal failure had a grave prognosis: median survival time was 95 days, mean survival 444 days. None of the known factors except age was associated with a worse outcome in CHF patients. LV/RV dysfunction, high plasma NT-pro-BNP, C-reactive protein, low albumin and body-mass index did not turn out to be prognostic indicators. The only factors indicating improved survival were recovery of renal function and low hemoglobin. CONCLUSION: Non-critically ill CHF patients with (sub-)acute renal dysfunction progressing to dialysis dependency have a grave prognosis. Renal failure itself had such a strong prognostic impact that conventional factors such as poor myocardial function or inflammation were concealed. Recovery of renal function and, surprisingly, anemia were beneficial factors. Alternative treatment strategies must be designed to improve the devastating prognosis for this special subset of patients with CHF.

Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure?

OBJECTIVE: Traditional cutoff values of serum creatinine considered to define postoperative acute renal failure have been challenged recently. In a previous investigation we demonstrated that minimal changes in serum creatinine concentration were associated with a substantial decrease in survival after cardiac surgery. In this investigation, we assessed the impact of minimal absolute increases in serum creatinine in a second institution, and we analyzed whether relative changes, as in the RIFLE classification and, partially, in Acute Kidney Injury Network (AKIN) classification, confer a different prognostic potential. DESIGN: Prospective analysis. SETTING: University hospital. PATIENTS: All consecutive patients undergoing cardiac surgery in the University Hospital of Zurich (Center USZ) over a 46-month period. INTERVENTIONS: Patients were prospectively documented. We analyzed maximal changes in serum creatinine in the first 48 hrs postoperatively (DeltaCrea) regarding death within 30 days. Results were compared with those of the University Hospital Vienna (Center AKH). Moreover, the prognostic potential of DeltaCrea within 48 hrs vs. serum creatinine elements according to RIFLE and AKIN classifications was assessed. MEASUREMENTS AND MAIN RESULTS: A total of 3,123 patients were evaluated from USZ. The majority of patients had decreased postoperative serum creatinine values (negative DeltaCrea) and the lowest mortality (1.8%). Minimal increases, [0, 0.5) mg x dL(-1), were associated with a more than doubled mortality in both centers (5%/6%). Mortality, according to RIFLE and AKIN classifications for both populations combined, was as follows: 7,023 (3.6%), 160 (29%), 43 (19%), and 15 (33%) for RIFLE Normal, Risk, Injury, and Failure; 6,644 (2.8), 463 (16.4), 3 (66.7), and 131 (1.8) for AKIN stage 0, 1, 2, and 3. CONCLUSIONS: Measuring repeat serum creatinine concentrations within 48 hrs and determining DeltaCrea were the most effective discrimination method to find patients at risk for adverse postoperative outcome after cardiac surgery, better than application of this sole criterion to the RIFLE (least discriminatory) or the AKIN classification.

Can we really predict the change in serum sodium levels? An analysis of currently proposed formulae in hypernatraemic patients.

BACKGROUND: Hypernatraemia is common in intensive care patients and may present an independent risk factor of mortality. Several formulae have been proposed to guide infusion therapy for correction of serum sodium. Unfortunately, these formulae have never been validated comparatively. We assessed the predictive potential of four different formulae (Adrogué-Madias, Barsoum-Levine, Kurtz-Nguyen and a simple formula based on electrolyte-free water clearance) in correction and maintenance of serum sodium in 66 hyper- and normonatraemic ICU patients. METHODS: With daily measurements of sodium/potassium and fluid/electrolyte balances, a day-to-day prediction of serum sodium levels was calculated using the four formulae. This was compared to the measured changes in serum sodium. RESULTS: Six hundred and eighty-one patient-days (194 hypernatraemic) in 66 patients were available for calculations. Prediction of serum sodium levels using all four formulae correlated significantly (P < 0.05) with measured changes in serum sodium. Individual variations were extreme, and the mean differences (+/-SD) for predicted versus measured serum sodium were within the range of 3.4-4.5 (+/-4.4-4.7) mmol/l similar for the Adrogué-Madias, Barsoum-Levine and Nguyen-Kurtz formulae. In comparison, our proposed formula underestimated the changes of serum sodium (mean +/- SD -1.5 +/- 5.3). During hypernatraemia, the differences between predicted and measured values were even greater (mean +/- SD 5.0-6.7 +/- 3.9-4.3) using the published formulae compared to our formula (mean +/- SD 0.2 +/- 4.0). CONCLUSIONS: Currently available formulae to guide infusion therapy in hyper- and normonatraemic states do not accurately predict changes of serum sodium in the individual ICU patient. In clinical practice, infusion therapy should be based on the reasons for hypernatraemia and serial measurements of serum sodium to avoid evolution of derangements.

Non-isotopic tyrosine kinetics using an alanyl-tyrosine dipeptide to assess graft function in liver transplant recipients - a pilot study.

BACKGROUND: Although accurate assessment of liver function in liver transplant recipients is of crucial importance for optimal timing of the procedure and for determining graft viability, none of the many available methods has proven reliable in the clinical routine. Thus, a novel non-isotopic assay of tyrosine kinetics using the tyrosine-containing dipeptide L-alanyl-L-tyrosine (Ala-Tyr) was tested for its clinical feasibility in patients undergoing orthotopic liver transplantation (OLT). METHODS: Plasma levels of tyrosine and clearance of tyrosine released after infusion of the dipetide Ala-Tyr were assessed before and one day after OLT in 10 liver transplant recipients with normal graft function, also in three organ donors and in three recipients showing poor graft function. Standard laboratory parameters (e.g. aminotransferases) and the plasma disappearance rate of indocyanine green were also measured. RESULTS: Following uneventful OLT, tyrosine plasma levels (before 127 +/- 15 micromol/vs. post-OLT 52 +/- 6 micromol/l, P < 0.05) and kinetics (tyrosine clearance: before 206 +/- 77 ml/min vs. post-OLT 371 +/- 109 ml/min, P < 0.05) were normalized. In cases of severe graft dysfunction, tyrosine kinetics (tyrosine clearance: 238 +/- 61 ml/min) resembled the situation in end-stage liver disease, whereas no such correlation was seen with conventional markers of liver function. Organ preservation had only a minor impact on tyrosine kinetics (n.s.). CONCLUSION: OLT rapidly normalizes both the plasma levels and the kinetics of tyrosine. Graft failure is associated with an immediate rise in plasma tyrosine levels and a delay in tyrosine elimination. Our results show that tyrosine clearance using the dipetide Ala-Tyr is a suitable non-isotopic, non-invasive indicator of graft viability in the early postoperative course following OLT.