Burn-related renal failure is usually seen in the initial resuscitation period after burn injury or as a component of severe sepsis-related multi-organ failure. The main factors responsible for the development of early renal failure in the burn patient are hypovolemia or an ineffective perfusion gradient between the glomerulus and Bowman’s space. The basic mechanism for the glomerular pressure/filtration ratio is effective renal blood flow, which is controlled by the relative resistance between the afferent and efferent arterioles. The main causes of decreased GFR in the early period are: 1- Hypovolemia 2- Myocardial depression (cardiac beat) 3- Extrinsic compression due to abdominal compartment syndrome 4- Protein denaturation may occur.
hypovolemia
The most common cause of early renal dysfunction in the burn patient is hypovolemia due to extravascular fluid loss from the wound site. Burns above 20% are sufficient for GFR reduction due to extravascular fluid loss (1,2). Decreased renal blood flow causes ischemia and cell death. Free oxygen radicals formed as a result of ischemia cause direct tubular epithelial damage and loss of tight connections between cells. Loss of tubule epithelium causes formation of casts within the lumen, obstruction, and ultimately a decrease in GFR. Therefore, the period when the kidneys are ischemic is critical for the development of renal failure. Nguyen et al. reported that the initial treatment in burn patients was effective on overall mortality. It has been reported that fluid replacement therapy is protective against the development of acute renal failure (3). In a similar study, it was reported that the time of initiation of fluid replacement therapy was associated with the incidence of acute renal failure and mortality rate. In the same study, it was reported that early aggressive fluid replacement therapy reduced kidney damage, prevented kidney failure, and had a positive effect on the clinical course (4).
Cardiac Dysfunction
It is known that heart failure causes renal failure by decreasing renal blood flow. Previously, the cause of heart failure in burn patients was attributed to reduced preload (preload) or hypervolemia, but today there is strong evidence that this is due to direct myocardial suppression. Heart failure that develops after burn injury is attributed by many physicians to the increased workload of the heart due to hypovolemic shock and electrolyte disturbances. Therefore, when starting fluid replacement therapy to correct the patient’s decreased renal perfusion, it is necessary to evaluate the patient’s cardiac reserve well and be careful in terms of signs of heart failure. Patients with a burn rate of more than 50% are at risk for myocardial ischemia and acute cardiac infection caused by extensive scar tissue due to decreased cardiac output and increased myocardial workload (5,6). Various theories have been developed to explain the decreased cardiac output associated with burn: • Increased sympathetic activity with impaired adrenal response • Myocardial ischemia as a result of hypovolemia • Direct myocardial suppression. Recently, direct myocardial suppression by tumor necrosis factor (TNF) has gained popularity among these theories. TNF is secreted by myocytes that are stimulated by endotoxin or by direct thermal injury. The effects of TNF on cardiac function include reversible biventricular dilatation, reduced ejection fraction and decreased sensitivity to catecholamines. Although early cardiac dysfunction due to TNF may benefit from inotropic support, the essential thing is to prevent the morbidity and mortality associated with kidney failure by preventing ineffective renal perfusion (7).
Abdominal Compartment Syndrome
Intravenous fluid resuscitation is required in burns greater than 20%. During fluid replacement, fluid transfers between the compartments. These fluid passages are especially dangerous when they occur in the third cavities such as the peritoneal cavity. Many studies on trauma patients have reported the negative effect of increased intra-abdominal pressure on visceral perfusion during fluid resuscitation. Abdominal compartment syndrome is mentioned when the intraperitoneal pressure is above 25 mmHg. Unfortunately, the frequency of this condition and the point at which visceral perfusion begins to decrease are not known exactly. In a study by O’mara et al., they showed that fluid replacement is a risk factor for abdominal compartment syndrome in burn patients. In cases where a crystalloid infusion over 25 L/kg is given, the clinician should be aware that cardiac output, renal perfusion and lung capacity will decrease and the risk of abdominal compartment syndrome is very high (8).
Protein Denaturation
Rhabdomyolysis and free hemoglobin have been implicated in the development of acute renal failure. Among them, it has been reported that rhabdomyolysis mostly causes kidney failure in burn patients. rhabdomyolysis; may occur following direct thermal injury, compartment syndrome, or electrical injury. The entry of myoglobin or free hemoglobin into the systemic circulation results in obstruction of the renal tubules, vasoconstriction in the afferent arterioles, and the resulting formation of free oxygen radicals. Free oxygen radicals cause renal failure by showing direct toxic effects on renal tubular cells. The degree of renal failure is directly related to the amount of iron-containing compounds entering the systemic circulation, the hydration status and the degree of acidosis. Fortunately, the incidence of renal failure due to protein denaturation is low and the prognosis is good if diagnosed and treated early (9).
sepsis
Since 1965, significant progress has been made in the treatment of burns. Early replacement and debridement treatment has improved the prognosis of burn-related acute renal failure. However, mortality due to renal failure secondary to sepsis still maintains its importance (10). Sepsis and septic shock are the most common causes of death in the intensive care unit. It is also responsible for 35-50% of acute renal failure in the intensive care unit. Some authors have reported that there is a direct relationship between the degree of sepsis and the incidence of acute renal failure (11). The key point in treatment is to know the pathophysiology of kidney failure. The etiology is multifactorial, but the main event begins with generalized arterial vasodilation due to a decrease in systemic vascular resistance. Initially, local cytokine release occurs directly at the site of invasion by the bacterium itself or its toxins. In sepsis, the balance between the production and destruction of these cytokines changes and the systemic production of these mediators increases. As a result of increased cytokine production, direct endothelial damage and vasoparalysis develops, resulting in a procoagulant state in the patient. Hypotension resulting from vasoparalysis stimulates the neurohumoral axis. The sympathetic system and the renin-angiotensin-aldosterone system respond to hypotension by increasing the cardiac output. However, this response directly causes renal arteriolar vasoconstriction, resulting in prerenal renal failure. This process is further complicated by the introduction of potent vasoconstrictors such as TNF and endothelin, and the suppression of local vasodilators (nitric oxide). As a result, the complement and fibrinolytic cascade is triggered and thrombophilia occurs in the patient. As a result of thrombophilia, disseminated intravascular coagulation may occur via glomerular microthrombus, which causes renal failure. The net effect on the kidneys is acute tubular necrosis due to renal ischemia resulting from decreased renal perfusion. Reduction in the amount of urine is the first and most common symptom. Urine amount has been shown to be a specific but non-sensitive marker. Many clinicians have reported that the amount of urine is insignificant in the diagnosis of renal failure. Because the extent of kidney damage can be serious without any change in the amount of urine. The reason for this is that the amount of urine is not determined only by GFR, but occurs depending on the difference between GFR and tubular reabsorption. Situations where the amount of urine helps in the diagnosis; anuria (<50 ml/day) or complete cessation of GFR (12). Severe prerenal insufficiency is the most common cause of anuria, excluding postrenal causes. Although conditions such as acute cortical necrosis, bilateral arterial occlusion or rapidly progressive acute glomerulonephritis may also cause anuria, the incidence of these causes is quite low and they are often distinguished from others by accompanying clinical findings. examination is very useful in diagnosis. Microscopic examination of urine sediment is a cheap, easy and very useful method (13). The presence of oliguria or anuria with normal urinary sediment suggests a prerenal cause, while the presence of epithelial casts and deformed tubular cells is pathognomonic for acute tubular necrosis. Similarly, the appearance of microscopic pigmented casts usually suggests myoglobinuria secondary to rhabdomyolysis. Evaluation of urinary electrolytes may be useful in diagnosis in cases where urine microscopy cannot diagnose.
Renal Replacement Therapy in Burnt Patients
Until recently, nephrologists recommended classical intermittent hemodialysis when renal replacement therapy was required in multi-organ failure. In the last 20 years, the concept of “critical care nephrology” has started to develop as a subgroup in severely affected patients. The main therapeutic procedure in this area has been determined as continuous renal replacement therapy (CRRT). CRRT has a very short history. Kramer accidentally placed the catheter in the femoral artery instead of the femoral vein for hemodialysis in 1997 and found that fluid elimination was possible due to the arteriovenous pressure gradient difference. Excess ultrafiltration was replaced by continuous infusion. This is called “continuous arteriovenous hemofiltration”. This is the first renal replacement therapy.
Effect and Application of Renal Replacement Therapy
; The main mechanism of action of RRT is the removal of inflammatory mediators, urea, creatinine and uremic toxins from the organism. It also provides fluid balance and a stable environment. 4 basic physics rules are used in RRT; ultrafiltration, convection, diffusion and adsorption. Inflammatory mediators (cytokines, thromboxane A2, leukotrienes and prostaglandins) are released as control substances in the defense mechanism of the organism. They act directly on the agent (which is often bacterial) without being specific, influencing the movement, differentiation and growth of immune cells. By playing a role in activating and inhibiting inflammation, they play a major role in limiting and eliminating inflammation. They provide a suitable environment for the repair of the affected organ. However, in cases such as multiple trauma, burns and septicemia, if the inflammatory response exceeds the goal, a diffuse inflammatory response occurs. Clinically, fever, circulatory disorder, procoagulation activity, development of DIC, ARDS, renal and hepatic insufficiency can be seen. In the laboratory, leukocytosis, high CRP, high lactate, decrease in albumin and AT III levels, thrombocytopenia, acidosis and biochemical changes depending on the affected organ can be seen. Widespread inflammatory response may lead to systemic inflammatory response syndrome (SIRS). The result of these is either MODS or MOF. Although the elimination capacity of RRT for inflammatory mediators varies depending on the membrane used, it can remove substances with a molecular weight in the range of 30,000-50,000 daltons (14). It should be 73m2/hour. The composition of the solution varies according to the patient. Today, the arterio-venous method, in which the heart acts as a pump, is not used. Instead, double lumen catheter and veno-venous methods are used. One of the main problems in RRT is to provide anticoagulation to provide adequate extracorporeal system. There is no fully biocompatible membrane that does not induce coagulation and does not itself secrete inflammatory mediators. Therefore, various anticoagulation methods are used according to the patient’s coagulation status; a- anticoagulation with heparin, b- anticoagulation with low molecular weight heparin, c- anticoagulation with 4% sodium citrate.
Most Commonly Used Modifications of RRT
Today, veno-venous continuous RRT is the most commonly used method. The most commonly used method for this is continuous veno-venous hemofiltration (CVVH). The basic physical principle in this method is convection. In CVVH, if the patient does not pass urine, large amounts of fluid can be drawn. Another method is continuous hemodiafiltration (CVVHDF). In this method, besides convection, diffusion, which is used in classical hemodialysis, is also used. CVVHDF is used when sufficient urea and creatinine cannot be cleared in CVVH. Since it is much slower than classical hemodialysis, there is no risk of disecilibrium syndrome. This method can imitate external renal functions very well (15).
RRT Indications
The kidney may be affected in cases of MOF, MODS, and SIRS. However, even in cases where the kidney is not affected, there is an indication for RRT so that inflammatory mediators do not damage other organs. Therefore, indications for RRT treatment in MODS patients can be divided into renal and non-renal.
Renal Indications
• The main indication is to eliminate renal hyperhydration with RRT in oliguric patients and to make room for parenteral nutrition and drugs. In addition, urea, creatinine, uremic toxins and cytokines are eliminated. Non-Renal Indications • Congestive heart failure unresponsive to diuretics • Septic shock with MODS and MOS, patients with sepsis • Patients with progressive SIRS before the development of MODS and MOF • Some intoxications • ARDS, prevention from tumor lysis syndrome
Disadvantages of RRT
Contraindications are not considered in critically ill patients. Because RRT can provide reversal of fatal disease. However, it may be necessary to minimize some complications and disadvantages before starting RRT. • Clinical findings may occur due to incompatibility of the material due to long-term contact of blood and membrane • Removal of glucose and amino acids by filtration • Tendency to bleeding and thrombocytopenia due to long-term use of anticoagulation and heparin • Heat loss due to extracorporeal system • Complications due to venous catheter • Cost of the application Intermittent hemodialysis in critically ill patients has several drawbacks. Since there is circulatory instability, sudden low blood pressure can be seen during the procedure. The reason for this is the sudden excessive fluid withdrawal, as well as the insufficient elimination of bicarbonate and inflammatory mediators in the solutions. In hemodialysis, intravascular urea decreases rapidly, but depending on the concentration gradient, urea is transferred from the extravascular space to the blood vessels and re-equibrium is formed. For this reason, it may be necessary to put the patient on hemodialysis treatment twice a day. While the mean urea level was 35 mmol/L in intermittent hemodialysis (HD) treatment, this value was 23.4 mmol/L in those receiving RRT. In the treatment of intermittent HD, 7 hours of HD daily is required to reach urea values like RRT. Although various mathematical models have been developed for the dose of RRT, the clinical practical significance of these methods has not been determined. The dose of RRT should be adjusted according to the clinical condition of the patient, not theoretical mathematical procedures. In multi-organ failure, the patient is at great risk. While mortality is 30-40% in two organ failure, this rate is 60-70% in three organ failure and 80-100% in four organ failure. Mortality rates can be reduced by 18-28% with RRT. Since controlled fluid withdrawal can be performed in RRT, this situation constitutes the decisive indication for RRT in many critically ill patients. A more dramatic response can be obtained with RRT in pulmonary edema and ARDS cases occurring in MOF and MODS cases in sepsis. Standard intermittent HD may be less effective because it is applied in the short term. Especially in cases where a large amount of fluid will be drawn, hypotension occurs much less with RRT. In cases where intermittent HD is applied, fluid cannot be completely withdrawn from the patient and hyperhydration occurs until the next HD treatment. Critically ill patients need 1.5-2 g/kg/day calories per day. RRT also helps to create enough space for the nutrition that the patient needs (16). Although it is stated in some publications that the mortality rates in patients who received RRT are the same as in patients who did not, such comorbidities are more common in patients who require RRT and RRT is required in patients with more severe burns. It is not right to come to a conclusion.
