**1.4 Serum creatinine**

sCr is an endogenous substance generated by the nonenzymatic conversion of creatine and creatine phosphate, 95% of which is found in the muscles [10]. sCr is an uncharged, small molecular weight, unfilled substance (113 Da) which is not related to whey protein. It is filtered freely by the glomerulus without tubular resorption. sCr is also secreted by the kidney tubules only in small quantities. In clinical practice, levels of sCr are used to determine kidney function to estimate the glomerular filtration rate. Its rise usually indicates either acute kidney injury (AKI) or chronic kidney disease [11, 12]**.** Due to the correlation between sCr levels and muscle mass, sCr in the steady state has been used as a surrogate of muscle mass measurements [13].

Low sCr levels could be considered as a proxy of protein-energy wasting in some clinical situations [14]. Individuals' sCr levels can be influenced by diet. In fact, arginine and glycine are precursors of creatine, and for this reason, a low protein intake in the diet can limit the generation of sCr. The sCr levels can be considerably lowered in the presence of protein malnutrition. Factors associated with low sCr levels are low muscle mass (female gender, elderly, and chronic illness), malnutrition, vegetarian diet, pregnancy, advanced liver disease, fluid overload, and augmented renal clearance.

AKI is an event that commonly complicates the clinical course of critically ill patients, contributing to multi-organ failure and requiring appropriate nutritional interventions in a strategic treatment.

The metabolic and nutritional demands of AKI patients are affected not only from the uremic state but also from the underlying pathology and complications associated.

A personalized approach for each patient that involves an analysis of specific nutritional requirements for each patient and a consideration of renal replacement therapy (RRT) support used is therefore necessary to improve the outcome of these patients.

Nitrogen is a fundamental component of the amino acids that make up the molecular structure of proteins. Proteins are the major functional substrate for cells and tissues and are essential for body growth and also for the maintenance and recovery. Protein metabolism generates calories (about 4 kcal/g). Nitrogen is released from protein degradation, which is also lost from secretions or excreted in sweat, feces, and urine. In particular, urea nitrogen represents 85–90% of the urinary nitrogen loss.

In the ICU patient, the greater non-urinary loss occurs through the intestine, severe burns, RRT, and/or by abdominal drains. The nitrogen balance becomes negative (from −5 to −30 g day), reflecting the important protein catabolism.

The nitrogen balance is calculated as the difference between the nitrogen intake and output, according to the following equation:

N balance protein intake g / die / 6.25 urinary = −+ ( ) nitrogen g / die skin / stool losses ( )

where skin/fecal losses are approximately 2–4 g per day, while urinary losses can be recorded in the urine for 24 h (or by sampling for at least 4 h). The equivalence between urea in mmol/l and g occurs via two parameters: urea (g) = urea (mmol)/20.36, and then through the fact that 6.25 g of protein contains 1 g of nitrogen (**Table 2**).

In the setting of inflammatory state, acute loss of kidney homoeostatic function plays a central role in the worsening of the dysmetabolic state of the condition of critical illness. The stress response also induces changes in the use of substrates:

• Cellular insulin resistance acquired and secondary to the reduction of translocation of GLUT4 transporters on the plasma membrane, contributing to hyperglycaemia and alteration of cellular energy

