Management of Chronic Kidney Disease and End-Stage Kidney Disease Patients in the Intensive Care Unit

Patients with Chronic Kidney Disease Who Develop Acute Kidney Injury

Increasing risk by as much as 10 times, CKD is the major risk factor for AKI development, particularly among critically ill patients admitted in the ICU. Although fluid overload and muscle wasting may affect the reliability of serum creatinine value in diagnosing AKI and staging its severity in critically ill patients, a transient decrease in renal function still may be recognized in most critically ill CKD patients. This transient form of AoC kidney dysfunction may be due to several mechanisms, including failure of autoregulation, abnormal vasodilation and adverse effects related to diuretics, antihypertensive agents, and/or nephrotoxins ( Fig. 214.1 ). Furthermore, the reduction of renal functional reserve (RFR) may increase the susceptibility of CKD patients to develop AKI, as well as the organ cross-talk feedbacks, in which the development of nonrenal organ dysfunctions resulting from or associated with CKD may lead to AKI.

RFR is the amount of renal clearance capability potentially available to counteract a metabolic stressful event. It may be quantified through the glomerular filtration rate (GFR) increase resulting from a kidney stress test, such as a protein load. Although still present, RFR is reduced progressively in worsening stage of CKD. In line with the RFR reduction, the extent of the minimum metabolic insult able to overcome the maximum achievable renal clearance is decreased progressively. In this context, the susceptibility of each CKD patient to develop AKI is directly proportional to the RFR reduction (see Fig. 214.1 ).

Beyond RFR, organ cross-talk (and mainly the cardiopulmonary-renal interaction) may explain the high incidence of organ dysfunctions in patients with CKD and their high incidence of AoC kidney dysfunction in the ICU. These interactions with pulmonary and cardiac functions are the most established in the literature (see Fig. 214.1 ).

As a matter of fact, CKD patients are at high risk to develop acute respiratory failure ( Fig. 214.1 , Panel A). Beyond the most intuitive mechanisms involving fluid overload and susceptibility to sepsis, several pathophysiologic pathways may explain the high incidence of acute or AoC respiratory failure leading to the ICU admission for these patients. For example, CKD has a major role in pulmonary hypertension development leading to pulmonary vascular remodeling through pathophysiologic mechanisms involving endothelial dysfunction, decreased bioavailability of nitric oxide, increased levels of endothelin-1, fluid overload, and shunting via arteriovenous fistulae. Furthermore, a lung structural remodeling may be recognized in CKD patients, mainly characterized by proliferation of fibroblasts with fibrosis and extracellular matrix deposition, resulting in thickening of the alveolar wall. In addition to the uremia-related dysfunction of the pulmonary microcirculation, these mechanisms may cause a restrictive, poorly compliant lung with impaired gas exchange ; moreover, the reduction in diffusion capacity for carbon monoxide correlates with the severity of renal impairment in CKD patients. All these mechanisms may reduce the lung functional reserve leading to increased susceptibility for acute respiratory failure and ICU admission.

As soon as the CKD patient develops acute or AoC respiratory failure, the possibility for AKI occurrence is increased exponentially. Several mechanisms sustained by organ cross-talk may lead to AKI coming from nonrenal organ damages ( Fig. 214.1 , Panel B). For example, most of patients with respiratory failure admitted in the ICU undergo mechanical ventilation that may have an effect on renal function; the hemodynamic effects of mechanical ventilation potentially leading to kidney hypoperfusion are well established in literature. In particular, positive pressure ventilation may lead to an increase in intrathoracic pressure, a reduced venous return, an increased vascular resistance in pulmonary circulation, right ventricular failure, cardiac septum shift, reduced left ventricle preload, reduced cardiac output, hypotension and peripheral hypoperfusion. All these hemodynamic effects may occur in patients with an already reduced kidney perfusion, directly related to the cause of respiratory failure (e.g., intraabdominal hypertension ), or for the concomitant alteration of neurohormonal pathway (e.g., those aimed at retaining salt and water to maintain an adequate vascular filling pressure to counteract the peripheral vasodilation resulting from hypercapnia). Furthermore, a well-established proinflammatory effect of mechanical ventilation has been associated with an increased susceptibility to develop clinical or subclinical AKI. Indeed, the production of inflammatory mediators, the expression of nitric oxide synthase, the induction of renal epithelial cell apoptosis, and the dysregulation of renal vascular response have been demonstrated to be associated with mechanical ventilation. The more RFR is reduced, the more precocious, severe, and persistent is the kidney damage occurring after all these processes.

Furthermore, CKD has been reported in up to 63% of cases of heart failure. An accelerated coronary artery atherosclerosis has been reported during CKD, through several mechanisms, such as hypertension, dyslipidemia, altered calcium/phosphorus metabolism, vascular remodeling, and increased vascular stiffness. Uremic cardiomyopathy has also a role in the structural and electrophysiologic heart remodeling, leading to biventricular hypertrophy, systolic and diastolic dysfunction, capillary rarefication, and cardiac fibrosis. The AoC uremic pericarditis with sterile effusion is a classical manifestation, although its occurrence is uncommon since the introduction of dialysis. Beyond these mechanisms, several factors may relate the incidence of acute heart failure to CKD ( Fig. 214.1 , Panel C).

The development of acute heart failure is a pivotal and progressive condition that leads to distant organ damage, because of interorgan cross-talk, whose severity is often proportional to the duration of heart failure. In these conditions, AKI occurs in about 25% to 33% of cases of acute decompensated heart failure (i.e., cardiorenal syndrome type 1 [CRS type 1]), whereas in 60% of them, an AoC kidney dysfunction may be diagnosed. Similarly, for what reported for the lung during respiratory failure, an impairment in cardiomyocytes potentially promotes distant organ damage (i.e., AKI); potential pathophysiologic mechanisms include ischemic and mechanical injury via innate immune system response, neurohormonal signaling, and release of metabolic products (i.e., catalytic iron) ( Fig. 214.1 , Panel D).

Acute Kidney Injury Patients Toward Chronic Kidney Disease

The analysis of the pathophysiologic continuum between AKI and CKD also includes the long-term worsening of the kidney function resulting from AKI. Several studies have underlined the incidence, causes, and pathophysiologic mechanisms of CKD/ESKD development after single or repetitive episodes of AKI. These studies have demonstrated consistently that, even when renal function is recovered after the acute insult, most of patients with AKI have a progression to advanced stages of CKD. Interestingly, this progression occurs even in absence of common risk factors (e.g., hypertension, diabetes, or cardiovascular disease ), during mild cases, and regardless of the cause of AKI. Although several pathophysiologic mechanisms leading to progression of renal damage in humans have been postulated in literature, the final causal pathways involved to the ongoing organ dysfunction seem to include maladaptive repair, disordered regeneration, or both (see Fig. 214.1 ).

Chronic Kidney Disease and End-Stage Kidney Disease Patients Admitted in the Intensive Care Unit

Advanced age and higher prevalence of peripheral vascular disease, cerebrovascular disease, ischemic and nonischemic cardiovascular disease, and diabetes mellitus are frequent comorbidities of CKD/ESKD critically ill patients. A recent systematic review demonstrated cardiopulmonary edema and sepsis as the most frequent causes for ICU admission in these patients. Common triggers of cardiopulmonary edema could be represented by pneumonia, excessive interdialytic weight gain, inappropriate prescription, and primary cardiac events. CKD/ESKD is associated with an increased incidence of critical illness and with a greater risk of morbidity and mortality after major surgical procedures.

Clinical Pictures

Major Surgical Procedures

Data on the possible impact of CKD/ESKD on outcome after major surgical procedures are scarce. For this reason it is not possible to perform a risk stratification of surgical patients. Patients with residual renal function before surgery and postoperative anuria have higher mortality rates than patients with no residual renal function before surgery or with residual renal function before and after surgery. Postoperative urine output is an important surrogate marker for kidney disease severity. In addition, perioperative hemodynamic status and biochemical factors are also related to patient's mortality.