Assessment of NGAL as an early biomarker of acute kidney injury in adult cardiac surgery patients.

Early and predictive acute kidney injury (AKI) markers may be decisive for the clinical outcome of heart surgery. Hence, this study set out to evaluate the biological variability of urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels in adult cardiac surgery patients, to test their feasibility as a biomarker of early AKI in a routine laboratory setting. uNGAL levels were measured with an automated immunoassay in urine samples from patients undergoing cardiac surgery using cardiopulmonary bypass, at the time of admission (T0) and 4 hours (T1) and 24 hours (T2) after surgery. Patients without post-operative AKI did not show significant differences in urine NGAL levels after surgery. In contrast, patients developing AKI displayed a significant increase (P=0.011) in uNGAL levels compared to T0. This increase was detectable at an earlier time point (T1, 4 hours) with respect to serum creatinine (T2, 24 hours). Confirming its utility as a biomarker, at T1 the uNGAL levels were significantly higher in AKI patients than in non-AKI patients (P=0.021). A receiver operating characteristic curve analysis of the uNGAL assay gave a sensitivity of 55.3 (95percent confidence interval, 26.59-78.73), a specificity of 72.9 (95 percent CI, 55.88-86.21), and a cut-off value for AKI prediction of 55.2. These results support the notion that urinary NGAL is an earlier marker of AKI than serum creatinine. However, the cut-off value of the assay was too low to consider it as a positive or negative diagnostic marker in AKI patients with moderate degree of severity. Likewise, its sensitivity and specificity were not high enough for it to be considered better than the others currently in use.

[Continuous renal replacement therapies (CRRT) will remain the most widely adopted dialysis modality in the critically ill]. / A favore delle CRRT: le terapie sostitutive renali continue rimarranno le metodiche prevalenti nelle unita' di terapia intensiva.

In the last 10-15 years, user-friendly continuous renal replacement therapy (CRRT) machines have played a major role in increasing the popularity of these techniques in intensive care settings. At present it is not clear which modality of renal replacement therapy (RRT) is optimal for critically ill patients with acute kidney injury (AKI). The choice between different modalities should therefore not be based on unproven ''outcome'' advantages but on evaluation of the clinical picture and logistical circumstances. In hypercatabolic patients, CRRT and sustained low-efficiency dialysis (SLED) have been shown to provide similar metabolic control, but uncontrolled studies suggested a better hemodynamic stability during CRRT, intended as a higher mean arterial pressure and/or less frequent need to increase inotropic or vasoactive drugs. The incidence of hemorrhagic complications is higher with CRRT; however, in particular conditions, such as in patients at high risk of bleeding, CRRT can be performed without anticoagulation or with the use of alternative anticoagulation protocols. Among the different modalities, regional anticoagulation with citrate appears to be the most promising, and the continuous development of simplified protocols for citrate CRRT might facilitate the more extensive use of this technique in the near future. The presence of a mismatch between prescribed and delivered dialysis dose is frequently reported as an important drawback of CRRT. However, data from a recent study designed to evaluate the prognostic impact of the intensity of renal support in critically ill patients with AKI showed that the target Kt/V was obtained in only 67-69% of intermittent hemodialysis (IHD) sessions. Data from several studies comparing the costs of different RRT modalities showed that CRRT is more expensive than IHD or SLED. However, the costs related to SLED can fluctuate within a wide range and in particular settings the higher costs of CRRT could be partially justified by logistical advantages. Further improvements in CRRT device characteristics, anticoagulation protocols, and adaptation of dialysis/replacement fluids to clinical needs will possibly contribute to maintaining, in the coming years, the key role of CRRT in the treatment of hemodynamically unstable critically ill patients requiring RRT.

[Acute renal failure following cardiac surgery]. / Insufficienza renale acuta post-cardiochirurgica.

Acute renal failure (ARF) develops in 1-30% of patients who undergo cardiac surgery and is associated with a high mortality rate (15-30%). Several risk factors (pre- and intra-operative) for ARF have been identified. Pre-operative factors are strictly related to cardiovascular disease, advanced age and baseline renal dysfunction, while intra-operative factors are linked with the type of cardiac surgery, the duration of cardiopulmonary bypass and aortic cross-clamping. These factors provide an opportunity to quantify the risk of ARF based on pre-operative data, and for this purpose a clinical score to predict post-operative ARF has recently been developed. Moreover, this score could allow the identification of those patients who may take advantage of preventive strategies. Mortality in patients who develop severe ARF requiring dialysis is particularly high (50-80%). Therefore, an early diagnosis of ARF and a timely and aggressive renal replacement therapy could improve the outcome.

[Pharmacokinetic principles and drug-dosing adjustments during continuous renal replacement therapies (CRRT)]. / Principi di farmacocinetica e aggiustamento posologico dei farmaci nell terapie sostitutive renali continue (CRRT).

In the critically ill, acute renal failure (ARF) and "Multiple Organ Dysfunction Syndrome" (MODS) can be associated with significant modifications of many pharmacokinetic parameters, such as protein binding, volume of distribution and total body clearance. The start of renal replacement therapy (RRT) represents an additional variable to take in consideration for drug-dosing adjustments. Drugs significantly eliminated by the kidney are likely to be removed during RRT and a supplemental dose or further dosing adjustments are required if extracorporeal clearance is more than 25-30% of total body clearance. The impact of RRT on plasma drug concentrations can be substantially different in relation to the type of treatment (diffusive, convective or both), membrane characteristics (low-flux or high-flux), filter surface area and prescribed dialysis dose. The molecular weight cut-offs of high-flux membrane are much higher than the molecular weight of most drugs. Therefore, molecular size will not be a limitation for the removal of the unbound fraction of the drugs most commonly used in the critically ill undergoing continuous renal replacement therapy (CRRT). However, diffusive clearance could be significantly lower than convective clearance for drugs in the middle molecular weight range. In any case, the extracorporeal clearances report-ed with the use of high-volume CRRT (>50-60 L/2 h) are often surprisingly elevated and can lead to drug underdosing in clinical conditions where adequate antibiotic treatment is essential.