**Abstract**

Skeletal muscle places a vital role in regulating immune function, glucose disposer, protein synthesis, and mobility. This massive dynamic reservoir of proteins, minerals, and other metabolites could be cannibalized, and a loss of skeletal muscle may predispose impaired tissue hailing and few poor immune functions. Several studies had shown the reduced survival rates and the increased hospital lengths of stay of patients who have a poor nutrition status and low muscle mass. In addition, few studies have demonstrated the effect of muscle wasting on serum creatinine. There are no data available regarding its effect on serum creatinine, and moreover, ICU-acquired myopathy is rarely recognized because of insufficient diagnostic criteria or methodological limitations. Despite these limits, serum creatinine is still considered the standard for assessing acute changes in renal function. The present chapter details the existing evidence related to the effects of nutritional status and muscle wasting on serum creatinine based on recent evidences.

**Keywords:** serum creatinine, muscle mass, muscle wasting, nutritional status

## **1. Introduction**

Skeletal muscle places a vital role in regulating immune function, glucose disposer, protein synthesis, and mobility. Unfortunately, critical illness is characterized by hypermetabolic and hypercatabolic states, which leads to an elevated resting energy expenditure rate, hyperglycaemia, altered substrate use, and increased oxygen consumption.

Among the patients who are previously well nourished before intensive care unit (ICU) admission, nutritional disorders develop rapidly because of the metabolic demands of illness, rapid fluid shifts, and the loss of specific vitamins and trace elements. Timely initiation of optimal nutritional support is important to slow the catabolic process and minimize adverse events such as prolonged mechanical ventilation, longer ICU stay, and increased risk of death [1]. The body's reaction to the illness (trauma, burns, inflammation, or surgery) includes an increase of energetic metabolism, hypersecretion of counter-regulatory hormones (glucagon, glucocorticoids, and catecholamines), and release of inflammatory mediators and other hormonal mediators (vasopressin) in the general setting of inflammation. Protein energy malnutrition is associated with muscle weakness, increased risk of infections, impaired wound healing, impaired coagulation

capacity, impaired gut function, reduced respiratory muscle function, and prolonged time to convalescence [2]. The present chapter details the existing evidence related to the effects of nutritional status and muscle wasting on serum creatinine (sCr) based on recent evidences.

### **1.1 Protein-energy nutritional status in intensive care**

The assessment of caloric and protein requirements include clinical history, nutritional history, physical examination, laboratory test (like albumin, prealbumin, blood glucose, transferrin, and kidney and liver function), severity of the illness, body mass index (BMI), ideal body weight (IBW), resting energy expenditure (based on calorimetry), and protein requirements (based on nitrogen balance). The nutritional assessment could be performed by direct calorimetry, performed by placing the patient in a calorimetric chamber, thermally insulated, in order to be able to evaluate the heat that it gives off by radiation, convection, conduction, and evaporation; this heat is detected by a water-cooled heat exchanger. Unfortunately, this method cannot be applied to all hospitalized patients. In critically ill, the gold standard is represented by indirect calorimetry, a method that measures respiratory gases: the oxygen of a determined volume of inspired air and the carbon dioxide produced. Therefore, numerous equations have been developed with the measurements performed with the indirect calorimetry in mechanically ventilated patients (**Table 1**).

Such equations use dynamic physiological variables, which allow the recalculation of energy expenditure, in order to evaluate how much energy the body spends in the acute phase, and then, determine the minimum requests. Predictive equations are notoriously inaccurate for individual critically ill patients, due to large differences in disease-related metabolic rate, treatment, and interindividual factors. Many centers that do not have indirect calorimetry adopt a simple approach providing 25–30 kcal/kg/day. Guidelines of the European Society for Clinical Nutrition and Metabolism recommend an intake of 25 kcal/kg/day in critically ill patients, and for both females than for males, considering, however, a 10–20% increase in patients with SIRS and overweight (BMI > 25), considering the IBW for calculation of energetic requirements [3].


*BSA, Body surface area; BW, body weight; H, height; Hb, hemoglobin; RR, respiratory rate; BT, body temperature; and TV, tidal volume; (a) Sex, 1 = man, 0 = female; Trauma, 1 = present, 0 = absent; Burn, 1 = present, 0 = absent; and Obesity, 1 = present, 0 = absent. (b) Sepsis, 1 = present, 0 = absent, based on clinical evidence of presumed infection, systemic inflammation, or organ dysfunction.*

#### **Table 1.**

*Predictive equations of energetic requirements (kcal/die) in critically ill patients.*

### **1.2 Muscle mass**

Skeletal muscle has emerged as a potent regulator of immune system function in regulating immune function, glucose disposal, protein synthesis, and mobility [4]. Skeletal muscle can be viewed as the dynamic storage depot of amino acid, which is sensitive to the fed and fasted states but also of minerals and other intermediate metabolites [5], which can be depleted to meet the need for other tissues involved in the inflammatory response. The loss of skeletal muscle and reduced protein storage may predispose to a relative glutamine deficiency, which is seen as impaired tissue healing, poor immune function, and reduced survival [5]. Significant changes in body composition occur with aging and are a consequence of imbalances between energy intake and needs associated with an increasingly sedentary lifestyle [6].

## **1.3 Lean body mass**

The body composition is often divided into fat mass and lean mass, the latter also known as lean body mass (LBM). LBM, unlike the fat mass that stores energy in the form of adipose tissue, includes muscle and visceral proteins and is mainly composed of water, proteins, glycogen, and minerals.

In pathological conditions such as chronic kidney disease (CKD), which is characterized by the presence of a positive water balance, it is necessary to perform an assessment of the volume of body water separately from the other components of the LBM. About half of LBM is made up of skeletal muscle mass, so the LBM compartment can be defined as heterogeneous and influenced by fluctuations in the distribution of water and electrolytes, which are more dynamic in nature in patients undergoing renal replacement therapy. Recent studies suggest that greater muscle mass is associated with greater longevity in people with chronic renal failure and in other chronic disease states [7]. Specific to LBM in the ICU, critically ill patients suffer significant LBM loss, much of it in the first 7–10 days of ICU stay [8]. However, patients gain weight back following ICU stay as fat mass but not as functional LBM [9]. Data in literature demonstrate that the catabolic/hypermetabolic state following injury can persist for up to 2 years following discharge from hospital, and this can markedly hinder the recovery of patients' LBM and function following injury [9].
