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18th ISAD

International Symposium on Albumin Dialysis

Renal and Liver Failure Management — ICU Perspective 2017 ISAD

Patients admitted to the hospital with liver failure often have concomitant renal failure.1 Unfortunately, renal failure is often unrecognized or is diagnosed late in the hospital course. Renal dysfunction progresses during hospitalization and is associated with increased morbidity, mortality and the development of chronic kidney disease.2 Serum creatinine grossly overestimated glomerular filtration rate in cirrhotics. Consequently, more stringent definitions allow acute kidney injury (AKI) to be recognized in the subpopulation.

Certainly, renal dysfunction may result directly from liver failure. This may be a consequence of hemodynamics, intrarenal hemodynamics, direct damage to the tubules and synergistic injury related to ongoing inflammation.3,4 Certainly, there is a spectrum of injury which progresses from hypoperfusion (pre—renal) to acute tubular necrosis with repeated episodes leading to fibrosis and chronic kidney disease. AKI is more likely in the setting of inflammation (SIRS) whether or not infection is manifest. However, infection frequently precipitates hospital admission for cirrhotics and is undoubtedly a direct and indirect cause of renal failure. 

Portal hypertension and malnutrition lead to hypoproteinemia, hypoalbuminemia, decreased oncotic pressure, ascites and anasarca. Circulating blood volume is decreased which compromises renal perfusion. Beta blockers make contribute to hypoperfusion, particularly later in the course of liver disease.5 Concomitantly, these same sequelae of liver failure increase renal venous pressure which contributed to kidney edema and lead to renal impairment.6 

Renal failure on presentation may reflect the interplay between acute insults and chronic renal failure. Furthermore, other causes of AKI may include medications such as antibiotics administered to patients with chronic liver disease.7 An aging and obese population means and increased prevalence of the metabolic syndrome with associated hepatic steatosis. Diabetic nephropathy and hypertensive nephrosclerosis should be considered as contributing to underlying chronic kidney disease. Kidney biopsy in the setting of liver failure frequently reveals structural abnormalities which reflect disease processes in addition to cirrhosis.8,9 

Delayed intervention compromises the potential for reversibility. This is often a consequence of not recognizing the severity of illness. ICU admission is therefore delayed. Key aspects of resuscitation include increase in renal perfusion pressure as a consequence of increased cardiac output, with appropriately increased preload; vasopressors to increase arterial tone and mean arterial pressure; and reduction in renal venous pressure by increasing intravascular oncotic pressure and decreasing intra-abdominal pressure. The latter may be accomplished with the removal of ascites and administration of hyperoncotic albumin. Choice of vasopressors is different in Europe and the United States. Terlipressin is preferred. However, norepinephrine is equally efficacious. Both are superior to the combination of octreotide and midodrine. 

Albumin likely has salutary effects in addition to increasing which reflect its anti-inflammatory capacity. Consequently, recognized infection in liver disease is best managed with rapid institution of antimicrobial therapy and administration of albumin. In this regard, rifaximin administered for management of hepatic encephalopathy may have both direct and indirect benefit: Allowing increased protein intake and improving nutritional status as well as decreasing enteric bacterial load. 

Adjunctive approaches are under investigation. These include dietary supplements such as carnitine and glutamine, and probiotics to restore the cirrhotic’s microbiota to normal. Dialytic therapy is often needed in the critically ill. However, timing remains controversial. Initiation may be of particular benefit in the patient with concomitant renal and hepatic failure as this will allow for appropriate fluid management and minimize volume overload. Albumin dialysis for example with the molecular adsorbent recirculation system (MARS®) which seem to offer specific benefit in patients with cirrhosis. Although the impact on survival is controversial, MARS® consistently improves hemodynamics allowing a reduction and vasopressors, consistently reduces hyperbilirubinemia and clears bile acids with the potential for reduction in cholemic nephropathy and improvement in mentation. Renal dysfunction in the critically ill as often associated with altered mentation (delirium). Improved neurologic function is likely to allow increased mobility and adequate protein intake thereby indirectly improving outcome. 

Acute kidney injury in the critically ill is associated with marked increase in morbidity and mortality. The same holds true and the impact magnified in the critically ill cirrhotic. However, recognition of the factors above argue for aggressive support including optimizing hemodynamics, instituting antimicrobials and dialytic therapy. The institution of early dialytic therapy will allow for recovery of intrinsic renal function and may be appropriate supportive care in the patient with cirrhosis with other causes for renal failure. In summary, early recognition of AKI offers an opportunity for prompt intervention to establish a diagnosis and to provide supportive care guided by critical care principles.

References:
1 Nadim MK, Durand F, Kellum JA, et al. Management of the critically ill patient with cirrhosis: A multidisciplinary perspective. J Hepatol 64:717‐735.

2 Wong F. The evolving concept of acute kidney injury in patients with cirrhosis
Nat. Rev. Gastroenterol. Hepatol. 12, 711–719 (2015); published online 20 October 2015; doi:10.1038/nrgastro.2015.174

3 Shum HP, Yan WW, Chan TM. Recent knowledge on the pathophysiology of septic acute kidney injury:
A narrative review. J Crit Care 2016; 31:82‐89.

4 Suarez‐Alvarez B, Liapis H, Anders HJ. Links between coagulation, inflammation, regeneration, and fibrosis in kidney pathology. Laboratory Investigation 2016; 96(4):378‐90.

5 Mandorfer M; Reiberger T. Beta blockers and cirrhosis, 2016. Digestive & Liver Disease 2017; 49(1):3‐10.

6 Gambardella I; Gaudino M; Ronco C; Lau C; Ivascu N; Girardi LN. Congestive kidney failure in cardiac surgery:
the relationship between central venous pressure and acute kidney injury. Interactive Cardiovascular & Thoracic Surgery 2016; 23(5):800‐805.

7 Pavkovic, Mira; Vaidya, Vishal S. MicroRNAs and drug‐induced kidney injury. [Review]. Pharmacol Ther 2016; 163:48‐57.

8 Wadei HM, Geiger XJ, Cortese C, Mai ML, Kramer DJ, Rosser BG, Keaveny AP, Willingham DL, Ahsan N, Gonwa TA. Kidney allocation to liver transplant candidates with renal failure of undetermined etiology: Role of percutaneous renal biopsy. Am J Transplant 2008 Dec; 8(12):2618‐26. PMID:19032225. DOI:10.1111/j.1600‐6143.2008.02426.x.

9 Wong, F. & Murray, P. Kidney damage biomarkers: novel tools for the diagnostic assessment of acute kidney injury in cirrhosis. Hepatology 2014; 60, 455–457.

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