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Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 microg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 microg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein belonging to the lipocalin superfamily. It was initially found in activated neutrophils, however, many other cells, like kidney tubular cells, may produce NGAL in response to various insults. Recently, it has been found to have a role in iron metabolism by virtue of its binding with siderophores. It has also been found to have a role in kidney development and tubular regeneration after injury. In experimental studies, it was found to be highly expressed in response to tubular injury. In subsequent clinical studies, urine NGAL has been found to be an early predictor for acute kidney injury (AKI). Newer devices for early bedside detection of NGAL are now available. Since serum creatinine is known to be an inadequate and late marker of AKI, NGAL might soon emerge as a troponin-like early marker for AKI. Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions.

A significant number of advancements have taken place since the beginning of continuous renal replacement therapy (CRRT). In particular, high volume hemofiltration and high permeability hemofiltration have been successful extensions of the technique. The additional and combined use of sorbent has also been tested successfully. Specific machines have now been designed to permit safe and reliable performance of the therapy. These new devices are equipped with a friendly user interface that allows for easy performance and monitoring. The apparent complexity of the circuit is made simple by a self-loading circuit or a cartridge which includes the filter and the blood and dialysate lines. Priming is performed automatically by the machine and pre- or postdilution (reinfusion of substitution fluid before or after the filter) can easily be performed by changing the position of the reinfusion line. These new machines permit all CRRT methodologies to be performed by programming the flows and the total amounts of fluid to be exchanged or circulated as a countercurrent dialysate at the beginning of the session. Progress has been made not only in technology in this area but also on our understanding of the pathophysiology of acute renal failure. New biomaterials and new devices are now available with new frontiers are on the horizon. We might, however, speculate that although improvements have been made, a lot remains to be done. There is no doubt that technology has progressed enormously in critical care nephrology and that more progress will come in the near future. The goal, and likely outcome, is an improvement in the morbidity and mortality of the most severely ill patients.

Summary Background and objectives The role of peritoneal dialysis in the management of AKI is not well defined, although it remains frequently used, especially in low-resource settings. A systematic review was performed to describe outcomes in AKI treated with peritoneal dialysis and compare peritoneal dialysis with extracorporeal blood purification, such as continuous or intermittent hemodialysis. Design, setting, participants, & measurements MEDLINE, CINAHL, and Central Register of Controlled Trials were searched in July of 2012. Eligible studies selected were observational cohort or randomized adult population studies on peritoneal dialysis in the setting of AKI. The primary outcome of interest was all-cause mortality. Summary estimates of odds ratio were obtained using a random effects model. Results Of 982 citations, 24 studies (n=1556 patients) were identified. The overall methodological quality was low. Thirteen studies described patients (n=597) treated with peritoneal dialysis only; pooled mortality was 39.3%. In 11 studies (7 cohort studies and 4 randomized trials), patients received peritoneal dialysis (n=392, pooled mortality=58.0%) or extracorporeal blood purification (n=567, pooled mortality=56.1%). In the cohort studies, there was no difference in mortality between peritoneal dialysis and extracorporeal blood purification (odds ratio, 0.96; 95% confidence interval, 0.53 to 1.71). In four randomized trials, there was also no difference in mortality (odds ratio, 1.50; 95% confidence interval, 0.46 to 4.86); however, heterogeneity was significant (I2=73%, P=0.03). Conclusions There is currently no evidence to suggest significant differences in mortality between peritoneal dialysis and extracorporeal blood purification in AKI. There is a need for good-quality evidence in this important area.

The cardio-renal syndromes (CRS) recently were defined systematically as disorders of the heart or kidney whereby dysfunction of one organ leads to dysfunction of another. Five types of CRS are defined. The first four types describe acute or chronic cardio-renal or renocardiac syndromes. Type 5 CRS refers to secondary cardio-renal syndrome or cardio-renal involvement in systemic conditions. It is a clinical and pathophysiological entity to describe the concomitant presence of renal and cardiovascular dysfunction. Type 5 CRS can be acute or chronic and it does not strictly satisfy the definition of CRS. However, it encompasses many conditions in which combined heart and kidney dysfunction is observed. Because this entity has been described only recently there is limited information about the epidemiology, clinical course, and treatment of this condition.

Background: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients. Methods: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed. Results: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01). Conclusions: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.

Incidence of acute kidney injury (AKI) is increasing rapidly to epidemic proportions. Development of AKI, especially in intensive care settings, is associated with increased morbidity, mortality and hospitalization costs. Currently available diagnostic tools are mostly insensitive for early diagnosis, however prompt diagnosis and risk stratification are necessary for guiding therapy and preventing progression of disease. Finding an early, reliable, suitable, easily reproducible, economical and accurate biomarker for AKI is a top research priority. In recent years, many urinary and serum proteins have been investigated as possible early markers of AKI and some of them have shown great promise. This topic reviews some of the emerging biomarkers of AKI.

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 microg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 microg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occured at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation.

All the vital organs of the body share information by virtue of various biological mediators. Primary pathology of a major organ can lead to dysfunction of the other. Cardiorenal syndrome is an important example of such organ crosstalk. Primary dysfunction of the heart or kidney can lead to injury of the other organ. As molecular injury occurs prior to clinical dysfunction, effective interventions can be planned if one can detect this organ dysfunction at an earlier stage by virtue of some biological markers. Such biomarkers can be substances in urine, serum, imaging maneuvers or any other quantifiable parameters. Some currently available biomarkers are not sensitive enough to provide timely diagnosis of the disorder. An important research priority is the development of newer biomarkers or a panel of biomarkers for the early diagnosis of organ dysfunction, as well as nature of injury, guidance for therapeutic interventions and prognosis. Many newer biomarkers have been studied for both heart and kidney dysfunction. This article focuses on newer biomarkers for the cardiorenal syndrome.

Systemic heparinization during continuous renal replacement therapy (CRRT) is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF) was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour) in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 patients including 42 males. Co-morbidities were comparable in both groups. HMARF was significantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 +/- 6.4 hours while it was 24.5 +/- 6.36 hours in heparin free group (P=NS). Patients receiving heparin had 16 bleeding episodes (0.45/patient) while only four bleeding episodes occurred in heparin free group (0.13/patient, P0.05). Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.

Many patients with heart failure have underlying renal dysfunction, and similarly, patients with kidney failure are prone to cardiac failure. This has led to the concept of cardio-renal syndromes, which can be an acute or chronic cardio-renal syndrome, when cardiac failure causes deterioration in renal function, or acute and/or chronic Reno-Cardiac syndrome, when renal dysfunction leads to cardiac failure. Patients who develop these syndromes have increased risk of hospital admission and mortality. Although there are clinical guidelines for managing both heart failure and chronic kidney disease, there are no agreed guidelines for managing patients with cardio-renal and/or Reno-Cardiac syndromes, as these patients have typically been excluded from clinical trials. We have therefore reviewed the currently available published literature to outline a consensus of current best clinical practice for these patients.

The incidence of acute kidney injury (AKI) formerly referred to as acute renal failure (ARF) is increasing to epidemic proportions. Development of AKI portends excessive morbidity and mortality. AKI is associated with prolonged hospital stay, increased healthcare costs and high mortality especially in critically ill patients. The mortality rate has remained largely unchanged for many decades. Delay in the diagnosis of AKI using conventional biomarkers like urine output and serum creatinine has been one of the important obstacles in applying effective early interventions. Several new biomarkers are being evaluated in a quest for early diagnosis of AKI, among which neutrophil gelatinase-associated lipocalin (NGAL) appears to be one of the most promising. This review summarizes the recent literature on these biomarkers.