Original chalk talk by Brandon Fainstad, MD
Edits, updates and graphics by Yilin Zhang, MD
- Differential of AKI in ESLD
- Pathophysiology of HRS (optional, ~ 7-10 min)
- Diagnosis and management of HRS
Teaching Instructions: This talk is designed as a chalk talk. Each figure takes you through a step of the chalk talk and new additions are highlighted in green. Click on each figure to find the teaching script for each step of the chalk talk. For earlier learners (med students and interns), there is a simplified diagram of the pathophysiology, diagnosis and treatment available.
There are also practice cases at the end which take ~ 5-10 min each.
Step 1: Differential of AKI in ESLD
Click for simplified pathophysiology, diagnosis and treatment of HRS.
Step 2: Pathophysiology of HRS (part 1)
Adapted from information/ figure from Bunyon, et al., 2009 in NEJM.
Step 3: Pathophysiology of HRS (part 2)
Adapted from information/ figure from Bunyon, et al., 2009 in NEJM.
Step 4: Diagnosis and Definition of HRS
Step 5: Treatment of HRS (Final Board)
TAKE HOME POINTS:
- AKI in patients with cirrhosis is most commonly caused by pre-renal etiologies and very rarely obstructive.
- HRS results in a prerenal AKI that does not respond to volume repletion.
- Lack of improvement in Cr after a 48 hour albumin challenge is suggestive of HRS.
- HRS is treated with volume expansion with albumin, vasoreactive medications (midodrine, octreotide) to raise the MAP. Only definitive treatment is liver transplant.
CASES (~ 15 min)
A 55 year old woman with HCV cirrhosis presenting with fever and increased confusion. Reports taking her lactulose as directed. Admits to increased abdominal girth but no pain, decreased UOP. Denies SOB, cough or dysuria. On exam, she is afebrile, HR 92, BP 92/60, 98% on RA. She is diffusely edematous with a distended, nontender abdomen. Labs are notable for:
- Na 127, BUN 30, Cr 2.4 (baseline 1.2)
- WBC 12, Hct 30, Plt 90
- Tbili 4 (baseline 2-3), alb 2
- UA: RBCs, hyaline casts
- Urine Na <10
What further work-up do you want?
She has a pre-renal cause of AKI – GI losses, sepsis, medications or HRS. She is coming in with acute decompensation of her chronic liver disease (worsening Cr, Tbili and worsening encephalopathy) and should be evaluated for spontaneous bacterial peritonitis (SBP). This can present without significant abdominal pain.
- Diagnostic paracentesis for SBP – showed 500 cells, 90% PMNs, gram stain shows PMNs only, culture is pending.
- An albumin challenge can be initiated to evaluate for HRS while awaiting results of other testing.
What is the cause for her AKI?
SBP! Greater than 250 PMNs on ascitic fluid cell count is suggestive of SBP. Empiric treatment should be started.
How are you going to manage it?
IV cefoxtaxime or ceftriaxone x 5 days. IV fluoroquinolones can be used in penicillin-allergic patients.
Albumin infusion 1.5 g/kg on day 1 and 1 g/kg should be used in patients with advanced liver or renal dysfunction – Tbili > 4, Cr > 1.0, BUN > 30. This has been shown to improve mortality and decrease risk of renal dysfunction4.
A 48 year old man with HCV/EtOH cirrhosis actively listed for transplant list presents from clinic with several lab abnormalities – worsening Cr, Tbili and INR. He reports increased fatigue, LE swelling and abdominal girth despite taking his diuretics. He reports mild abdominal diffuse abdominal discomfort but denies fever, chills, cough, SOB or dysuria. On exam, he is afebrile, HR 60, 92/45, 96% RA. He is diffusely edematous with a tight distended abdomen. Labs are notable for:
- Na 126, BUN 40, Cr 2.4 (baseline 1.0 from 1 month prior)
- WBC 8, Hct 28, Plt 80
- Tbili 11 (baseline 4), INR 5 (baseline 2)
- UA: 1+ protein, hyaline casts, occasional granular casts
- Urine Na>65, FeUrea 30%
What additional work-up do you want?
FeUrea should be used in place of FeNa when patients are on diuretic therapy (which will cause urinary sodium excretion, resulting in high urine Na). FeUrea <35% is suggestive of pre-renal cause of AKI – GI losses, sepsis, medications or HRS.
Of note, ATN can be difficult to distinguish from other causes of AKI in patients with ESLD. Granular casts can be seen in the setting of severe hyperbilirubinemia and are not specific to ATN. FeNa and urine Na can be low even in the setting of ATN given persistent activation of renin-angiotensin-aldosterone system in advanced cirrhosis (aldosterone reclaims Na from urine).
He is presenting with acute decompensation of her chronic liver disease (worsening Cr, Tbili, Tbili and worsening ascites). He should be further evaluated with:
- Diagnostic paracentesis for SBP – showed 450 cells, 10% PMNs
- RUQ US with duplex for portal vein thrombosis (PVT) given worsening ascites – negative for PVT
- Consider Foley placement to measure bladder pressure to evaluate for abdominal compartment syndrome – bladder pressure 12 mmHg (normal)
- Albumin challenge for HRS – no improvement in Cr after 1 g/kg albumin x 48 hr.
What is the cause for this patients AKI?
He has HRS given non-response to albumin challenge, likely type II given Cr < 2.5. Reviewing trend of Cr can point towards type I or type II. Type II HRS is commonly associated with refractory ascites3.
How are you going to manage this?
- Stop his diuretics, his volume can be managed with periodic paracenteses
- Albumin up to 40 g/day for additional volume expansion
- Midodrine 5 – 7.5 mg TID as a starting dose with goal increase in MAP > 15 mmHg
- Octreotide 100 μg SQ TID
His cirrhosis is too advanced to consider TIPS should he not respond to this therapy.
Definitive therapy is a liver transplant (fortunately, he’s already listed!). The kidney transplant team should also be involved in the management of his HRS. In some cases, patients require a concurrent liver-kidney transplant for severe HRS.
A 45 year old man with PSC cirrhosis presenting to the ED with increased abdominal pain typical of his PSC flares. The pain has been going on for about a week and he was initially managing it with OTC pain medications (Tylenol and ibuprofen) but has progressively worsened. He denies fevers/chills, cough or abdominal pain. He reports decreased UOP and darker colored urine. On exam, he is AF, HR 90, BP 120/80, 98% RA. He has a non-distended abdomen with mild RUQ tenderness without a Murphys’ sign. He has no CVA tenderness. Labs are notable for:
- Na 132, K 5.8, Cr 3.6 (baseline of 0.9)
- WBC 6, Hct 32, Plt 110
- Tbili 4 (baseline of 3), INR 1.4
- UA: hyaline casts, 1+ WBC
- Urine Na 28, Urine Cr 60
What is the likely cause of this man’s AKI?
He has an intrinsic/renal cause of AKI. His FeNa is 1.5%. With + WBCs on UA and recent heavy NSAID use, we have a high suspicion for AIN (acute interstitial nephritis).
How do you want to manage him?
- Stop offending medications – NSAIDs
- Volume challenge – reasonable to give a volume challenge to patients with AKI without signs of significant volume overload to rule out any concurrent pre-renal etiology. This is especially useful in this case given that NSAIDs also cause a pre-renal AKI and he may have had decreased PO in the setting of recent PSC flare.
- Regner, KR & Singbartl, K. Kidney Injury in Liver Disease. Crit Care Clin. 2016. 32; 343-355.
- Ge, PS & Runyon, BA. Treatment of Patients with Cirrhosis. NEJM. 2016;375:767-77
- Liou, IU. Management of end-stage liver disease. Med Clin North Am. 2014 Jan;98(1):119-52.
- Sort, P, et al. Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis. NEJM. 1999; 341:403-409.
- Runyon, BA. Renal Failure in Cirrhosis. NEJM. 2009; 361(13):1279-1290.