Today's case involved a middle-aged person with cirrhosis, hepatocellular carcinoma, and a variceal upper gastrointestinal bleed. The patient was admitted to critical care for banding of bleeding varices, and then transferred to the ward. Shortly thereafter, her creatinine began to rise. We spoke about the multiple possible etiologies for her acute kidney injury.
-We spoke about the creatinine itself as a renal marker. The principle things affecting the serum creatinine are the production of it (predominantly muscle mass which is severely reduced in cirrhotic patients) and its elimination (through the kidney). Theoretically sudden muscle catabolism would make the serum creatinine rise independently of renal function. Additionally, the serum creatinine level must be steady state for it to be a reasonable estimate of the GFR. If both renal arteries are clamped, the creatinine will rise slowly over several days while the GFR has actually been reduced to zero. Likewise, if the creatinine is 1000 and the renal artery clamps are remove, the GFR returns to normal, but the creatinine will take several days to fall back down.
-Acute Kidney Injury can be divided simplistically into three general causative mechanisms.
-Pre-renal AKI occurs as a result of insufficient renal blood flow and, by definition, corrects completely when renal blood flow is restored. This can occur most commonly as a result of volume contraction, third spacing, or impaired forward flow. Cardiorenal syndrome and hepatorenal syndrome are, from a kidney standpoint, mainly types of pre-renal AKI. Vascular obstructions can also lead to this phenomenon.
-Post-renal AKI occurs as a result of impaired urinary outflow from the kidneys. With two healthy kidneys, unilateral obstruction (as in the case of nephrolithiasis) is unlikely to cause this. Obstructions at the level of the bladder or prostate may do this. The general treatment is restoring urine flow through catheterization or nephrostomy tubes.
-Intrinsically renal AKI is a detailed discussion, but can be simplified into which part of the kidney is experiencing the problem. The glomerulus can be injured by a variety of mechanisms including infections (post-streptococcal, hepatitis B, hepatitis C, HIV), autoimmune processes like SLE, and neoplastic process like Hodgkin disease. The renal tubules can be injured by medications or ischemia. The most common tubular disorder is acute tubular necrosis, which most often results from prolonged periods of reduced renal blood flow leading to the death of tubular cells. They slough off and create a characteristic muddy brown (heme granular) cast. The renal parenchyma can be injured by drugs, autoimmune disease, or chrnonic infections (acute/allergic interstitial nephritis) and, although no findings are characteristic for this condition, may show WBC casts in the urine or eosinophiluria.
-Ultimately, this patient was diagnosed with hepatorenal syndrome, which is often a harbinger of a poor outcome.
-Hepatorenal syndrome can be divided into two types. Type 1 HRS is the more serious type, where large acute rises in creatinine lead to a need for either palliative management or liver transplantation. Type 2 HRS is a less severe renal impairment wherein patients usually develop diuretic-refractory ascites. Their creatinine slowly creeps up in contrast to type 1.
-There are a number of requirements when making a diagnosis of HRS:
· Chronic or acute liver disease with portal hypertension and advanced liver failure
· An acute kidney injury with a rise in creatinine of >26.5umol/L or 50% within 7 days
· The absence of an apparent other cause – this means that shock, nephrotoxins, spontaneous bacterial peritonitis, and systemic hypovolemia must be excluded.
· The absence of more than 50 RBC/hpf on microscopy
· Urine protein excretion < 500mg/day
· Lack of improvement with intravenous albumin (1g/kg) for two days
· Withdrawal of diuretic therapy
-As we mentioned, the urinary sodium off the diuretics is typically very low (<20mmol mmol--="">20mmol>
-To treat HRS, the protocol varies between critical care and medicine. When the patients are in critical care units, they can receive intravenous norepinephrine and intravenous albumin for the combined purpose of volume expansion (with colloid likely to stay intravascular) and splanchnic vasoconstriction to improve renal blood flow. When patients are on the wards, they are usually treated with intravenous albumin, octreotide infusions, and oral midodrine (also a vasopressor). In the USA, a drug called terlipressin is available which can be used instead.
-Often, these patients deteriorate. If they are not candidates for liver transplantation, then aggressive medical therapy may be their only hope – sometimes that fails and palliation/symptom control needs to be considered. Many nephrologists do not offer dialytic therapy to these patients because their underlying liver condition is not reversible. Occasionally, patients are transplant candidates and may be dialyzed as a bridge to transplantation.
Ginès, P., & Schrier, R. W. (2009). Renal failure in cirrhosis. New England Journal of Medicine, 361(13), 1279-1290.
Image Credit: Ginès and Schrier, 2009 (above).
Gluud, L. L., Kjaer, M. S., & Christensen, E. (2006). Terlipressin for hepatorenal syndrome. The Cochrane Library.