Acute kidney injury in patients with cirrhosis: perils and promise

Abstract

A 62-year-old man with cirrhosis secondary to hepatitis C and chronic alcohol abuse was admitted to the intensive care unit with hematemesis and mental status changes. Physical examination showed ascites and stigmata of chronic liver disease. Blood pressure was noted as 87/42 mm Hg and laboratory studies showed a serum creatinine level of 0.8 mg/dL, an estimated glomerular filtration rate of 84 mL/min/1.73 m(2) calculated using the Modification of Diet in Renal Disease Study equation, a serum sodium level of 123 mEq/L, a total serum bilirubin level of 4.3 mg/dL, and an international normalization ratio of 1.6. The patient was resuscitated with packed red blood cells and fresh-frozen plasma and bleeding was controlled. However, on the third day of admission, creatinine level increased to 1.5 mg/dL. Examination of urine sediment showed 1 to 5 bilirubin-stained granular casts per high-powered field and a few renal tubular epithelial cells. The urine sodium level was 21 mEq/L and the fractional excretion of sodium was 0.43%.

Keywords: AKI; AKIN; ATN; Acute Kidney Injury Network; Acute Tubular Necrosis; Ascites; CKD; Cirrhosis; FENa; GFR; HRS; Hepatorenal; IAC; ICU; International Ascites Club; KIM-1; Kidney Injury; MDRD; Modification of Diet in Renal Disease; NGAL; OR; PRA; RAAS; Urinary Biomarkers; acute kidney injury; acute tubular necrosis; chronic kidney disease; fractional excretion of sodium; glomerular filtration rate; hepatorenal syndrome; intensive care unit; kidney injury molecule-1; neutrophil gelatinase–associated lipocalin; odds ratio; prerenal azotemia; renin-angiotensin-aldosterone system.

Figure 1. Precipitants, mechanisms and clinical correlates of hepatorenal syndrome and acute tubular necrosis in cirrhosis

Portal hypertension leads to splanchnic and systemic vasodilatation, decreasing effective arterial blood volume. This decrease stimulates activation of SNS, RAAS and ADH with resulting retention of sodium and water, increaseing cardiac output, ascites and hyponatremia. The increased activity of vasoconstrictor systems also causes renal vasoconstriction and chronically decreased renal perfusion. Any factor that worsens vasodilatation (infection, LVP, vasodilators) or decreases blood volume (diarrhea, overdiuresis, bleeding) can decrease renal perfusion further and lead to AKI. In advanced cirrhosis, splanchnic vasodilatation and renal vasoconstriction can become refractory to volume expansion and, compounded by decreased cardiac function (akin to high output heart failure), lead to severe renal hypoperfusion and development of hepatorenal syndrome. Alternatively, precipitants may be severe enough to produce structural tubular injury (e.g. septic or hypovolemic shock) and acute kidney injury. The extent to which prolonged, severe hepatorenal syndrome can progress to acute tubular necrosis remains unclear and is thus depicted with a dashed line. Abbreviations: LVP, large volume paracentesis; SVR, systemic vascular resistance; MAP, mean arterial pressure; GI, gastrointestinal; SNS, sympathetic nervous system; RAAS, renin-angiotensin-aldosterone system; ADH, anti-diuretic hormone; NSAIDS, non-steroidal antiinflammatory drugs; GFR, glomerular filtration rate

Figure 2. Extra-renal influences on serum creatinine levels

Primary extra-renal influences on serum creatinine are depicted. In addition to the status of renal filtration, creatinine levels are affected by factors that influencing its production and excretion as well as those that impact its measurement. Factors especially relevant to patients with cirrhosis are depicted in red.

Figure 3. Degree of AKI progression and mortality

Progression is defined by an increase in AKIN stage after initially fulfilling AKIN criteria. Progression to dialysis refers to any patient who presented as non-dialysis dependent but subsequently developed the requirement for dialysis. (Reproduced with permission from Hepatology 2013;57(2):753–762)

Figure 4. Nephron localization of kidney injury biomarkers

Primary sites of production for the most extensively studied biomarkers of kidney injury. Abbreviations: KIM-1, kidney injury molecule-1; L-FABP, liver-type fatty acid binding protein; IL-18, interleukin-18, NGAL, neutrophil gelatinase associated lipocalin