Understanding acute kidney injury in cirrhosis: Current perspective

Abstract

Acute kidney injury (AKI) is present in 30%-40% of hospitalized patients with cirrhosis. Its incidence is higher in patients with severe alcoholic hepatitis, spontaneous bacterial peritonitis, and acute-on-chronic-liver failure (ACLF). Kidney injury is an important landmark event in the natural history of cirrhosis as it is associated with higher mortality. Overwhelming systemic vasodilation, cardiac dysfunction, hypoperfusion, endotoxemia, and direct nephrotoxicity predispose patients with cirrhosis to kidney injury. Infection is present in 25% of patients with decompensated cirrhosis and 35%-40% of patients with ACLF. Advanced cirrhosis with portal hypertension leads to a sluggish portal flow, leading to increased gut congestion, altered gut permeability and bacterial translocations. They drive infection and endotoxemia in such patients. Pathogen-associated molecular patterns activate inflammatory cascades, which leads to further deterioration in hemodynamics and reduced glomerular filtration rate. Infections and pro-inflammatory cytokines like interleukin 6 (IL-6), IL-1, and tumor necrosis factor alpha may directly cause kidney parenchymal injury. The combined effect of dysfunctional albumin and systemic and splanchnic vasodilatation leads to low effective blood volume, activating the renin-angiotensin-aldosterone system. This causes renal vasoconstriction, water retention, and ascites, which progresses to hepatorenal physiology and AKI development. Vasoconstriction and volume expansion effectively improve arterial blood volume and systemic hemodynamics, thereby improving renal blood flow. It is of paramount importance to predict, detect, and treat AKI in its early state, as progressive renal dysfunction is invariably associated with higher mortality in patients with decompensated cirrhosis and ACLF. This comprehensive review will focus on the recent evolving concepts of the pathophysiology, diagnosis, and management of AKI in patients with cirrhosis.

Keywords: Acute kidney injury; Acute-on-chronic liver failure; Ascites; Cirrhosis; Hepatorenal syndrome.

Figure 1

Altered hemodynamic and targets of therapy in patients with acute kidney injury in cirrhosis. Increased intestinal permeability allows gut-derived lipopolysaccharides to enter the systemic circulation. Overwhelming systemic vasodilatation leads to a decrease in systemic vascular resistance and effective blood volume. Underfilling of the renal vasculature activates the renin-angiotensin-aldosterone system (RAAS) axis. RAAS activation leads to sodium retention, reduced glomerular filtration rate, and ascites. The quantitative defects in albumin contribute to decreased oncotic pressure and further worsen hemodynamics. Hence, albumin, along with splanchnic vasoconstrictors, is the mainstay of treatment in patients with hepatorenal syndrome. AKI: Acute kidney injury; EABV: Effective arterial blood volume; GFR: Glomerular filtration rate; PAMPs: Pathogen-associated molecular patterns; RARI: Renal artery resistive index; SVR: Systemic vascular resistance.

Figure 2

Stepwise diagnostic algorithm of acute kidney injury in patients with cirrhosis. Routine and microscopic examination of urine, 24-hour urinary protein, and fraction urinary sodium excretion are the initial diagnostic modalities. Bedside point-of-care ultrasound, renal artery resistive index, and newer biomarkers can be used as additional supportive evidence to pinpoint a diagnosis of acute kidney injury (AKI) in cirrhosis and classify them. After acute interstitial nephritis and glomerulonephritis have been ruled out, volume expansion therapy with albumin is advocated. Patients who fail to respond to albumin after 48 hours of therapy should be classified as hepatorenal syndrome (HRS). Based on the last serum creatinine, they can be classified as HRS-AKI or HRS-non-AKI. AKD: Acute kidney disease; ATN: Acute tubular necrosis; CKD: Chronic kidney disease; e-GFR: Estimated glomerular filtration rate; HRS-NAKI: Hepatorenal syndrome-non-acute kidney injury.