Trevor R. Smith, MD Northern Utah Kidney Specialists University … · 2019-05-07 · Trevor R....

Trevor R. Smith, MDNorthern Utah Kidney Specialists

University of UtahDepartment of Medicine

Division of Nephrology and Hypertension

Northern Utah Kidney Specialists

I have no financial relationships with any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.


• The Learner will recall the pathophysiology of decompensated cirrhosis and hepatorenal syndrome.

• The Learner will explain the evaluation and management of hepatorenal syndrome.

• The Learner will apply objective data when managing ascites due to decompensated cirrhosis.



• Complications of decompensated cirrhosis such as AKI, ascites, varices, cirrhotic cardiomyopathy and others occur because of:

a) Increased circulatory state by activation of the sympathetic nervous system, RAAS activation and increased ADH

b) Decreased systemic vascular resistance by release of systemic vasodilators

c) Decreased hepatic clearance of vasoactive metabolites such as renin, angiotensin II, aldosterone and vasopressin

d) A and Be) A and Cf) B and Cg) A, B and C

• Definition: diffuse liver fibrosis and abnormal nodules that lack normal organization. The structural changes result in portal hypertension and impaired liver function.


Lancet 2008; 371: 838–51

↓ clearance of: ANP, Glucagon, Renin, ATII, VP,

Aldo

Northern Utah Kidney SpecialistsLiver Int. 2018;38(4):570


SNS, RAAS, ADH

SVR & Effective circulating volume,MAP, HR, CO

VEGF, NO Vasodilators

Hepatol Int. 2018;12(Suppl 1):112

• Compensated: ↑ CO and plasma volume restores ECV.

• Decompensated:↑ vasoconstriction to keep ECV → ascites and renal failure.


• √ The Learner will recall the pathophysiology of decompensated cirrhosis and hepatorenal syndrome.



• AKI occurs in up to 50% of patients with decompensated cirrhosis

• 46% infection, • 32% hypovolemia, • 13% HRS and • 9% intrinsic kidney disease

• 1/3 of patients improve with conservative management• Albumin, IVF

• 2/3 develop persistent renal injury• 40% require dialysis• 60% mortality by 90 days

CJASN 2018, 13(1):16-25.


• A 63 yo M with a 30 year history of EtOH abuse presents to the ER with hematemesis. On examination BP is 74/46 mmHg. His abdomen is distended and tense. Labs reveal a serum sodium of 121, BUN 124, serum creatinine of 3.6 (baseline unknown), T bili24.1, elevated transaminases and a Hgb of 6.8 g/dL.

Treatment of this patient with probable acute kidney injury includes:

a) Transfusion of pRBCs and urgent EGD to evaluate for esophageal varices

b) Diagnostic paracentesis with cell count and culture to evaluate for SBPc) Discontinuing all diuretics and antihypertensive medicationsd) Administration of IV albumin and octreotidee) Administration of vasoconstrictors such as midodrine or

norepinephrine to target a MAP of >82 mmHgf) All the above


Clin Gastroenterol Hepatol.2018;16:162

https://www.ncbi.nlm.nih.gov/pubmed/28602971


• ATN: Granular casts, urine osm = serum osm• Nephritis: Proteinuria and hematuria• CKD: baseline Cr, proteinuria, comorbid conditions• Other: Check renal ultrasound for evidence of

abnormal anatomy or obstruction

https://radiopaedia.org/articles/pelviureteric-junction-obstruction-1?lang=ushttps://webpath.med.utah.edu/TUTORIAL/URINE/URINE.html#2

https://radiopaedia.org/articles/pelviureteric-junction-obstruction-1?lang=us

https://webpath.med.utah.edu/TUTORIAL/URINE/URINE.html#2


• Diagnosis of exclusion1.Cirrhosis + ascites2. Serum creatinine >1.5 mg/dL3. Not better after 48+ hours of:

-Diuretic withdrawal -Albumin expansion

4. No shock.5. No current or recent treatment with nephrotoxic drugs (?)6. Absence of parenchymal kidney disease

-Proteinuria >500 mg/day, -Microhematuria (>50 RBCs/high power field)-Abnormal renal ultrasound scanning

http://www.icascites.org/about/guidelines/



• Type-1 HRS • Rapid renal failure = 2x serum creatinine to a level greater

than 2.5 mg/dL in <2 weeks.• Precipitating event, ie SBP

• Can occur spontaneously• Acute arterial hypotension → activation of vasoconstrictors

which leads to rapid impairment in liver function and encephalopathy




• Type-2 HRS • “Moderate” renal failure (serum creatinine >1.5 mg/dl)

progressing slowly. • Spontaneous, less association with SBP• Frequent refractory ascites. • Survival

• Ascities without renal failure > HRS type 2 > HRS type 1



• ICU v Non-ICU• ICU- treatment with Norepinephrine + Albumin

• +/- Vasopressin• Non-ICU- treatment with Midodrine + Octreotide + Albumin

• Upcoming therapy: Terlipressin


Northern Utah Kidney SpecialistsGastroenterol Hepatol (N Y). 2015 Apr; 11(4): 220–229.

Ornipressin & Terlipressin: analogs of ADH that cause

preferential splanchnic vasoconstriction

OrOctreotide – somatostatin mimic that decreases splanchnic blood

flowAlbuminMAP Midodrine

Norepinephrine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4836593/

• Norepinephrine + Albumin


Hepatology. 2002 Aug;36(2):374-80.

https://www.ncbi.nlm.nih.gov/pubmed?term=12143045

• Octreotide + Midodrine + Albumin


Dopamine + Albumin Octreotide + Midodrine + Albumin

Hepatology. 1999;29(6):1690.

• Octreotide + Midodrine + Albumin


Dig Dis Sci. 2007 Mar;52(3):742-8.

https://www.ncbi.nlm.nih.gov/pubmed?term=17235705


Clin Gastroenterol Hepatol.2018;16:162

https://www.ncbi.nlm.nih.gov/pubmed/28602971


56%

5%

Hepatology. 2015 Aug;62(2):567-74.

CR + PR

CR + PR

CR

CR


Hepatology. 2015 Aug;62(2):567-74.


Gastroenterology. 1988 Feb;94(2):482-7


Gastroenterology. 1988 Feb;94(2):482-7

>2.8 g/dL

≤ 2.8 g/dL


Terlipressin + albumin v Albumin alone

Terlipressin + albumin v Norepinephrine + albumin

Journal of Clinical Gastroenterology. 52(4):360–367, APR 2018

• Terlipressin + Albumin• Not available in US, awaiting results of Phase 3 trial

(CONFIRM Study)



J Fernández, V Arroyo. Hepatorenal Syndrome. Comprehensive Clinical Nephrology, 5th Edition. 873-882.





flowAlbuminMAP Midodrine



Entire cohort of 91 cirrhotic patients with HRS type 1

Child-Pugh score <10

Child-Pugh score ≥10


Renal Replacement Therapy Transjugular Intrahepatic Portosystemic Shunt

(TIPS)

P=0.961 P=0.034


P=0.000

Response to therapy


CJASN January 2018, 13 (1) 16-25

Northern Utah Kidney SpecialistsCJASN January 2018, 13 (1) 16-25

• High suspicion for HRS• Other causes more likely

• Volume resuscitate with albumin, discontinue diuretics and BP meds

• Treat underlying problem, • Infection or bleeding

• Look for kidney disease• BP target = MAP > 82 mmHg

• Midodrine/octreotide OR norepinephrine• Terlipressin is the future?

• Dialysis for patients eligible for liver transplant



• √ The Learner will explain the evaluation and management of hepatorenal syndrome.



• Your 63 yo M with EtOH hepatitis and AKI responds to midodrine/octreotide/albumin and banding of esophageal varices. He is discharged to acute rehab. He is not a transplant candidate because he stopped EtOH on hospital admission. While in rehab he continually experiences abdominal discomfort and distension. Abdominal ultrasound and physical examination reveals the presence of tense ascites.

Besides encouraging sobriety, how do you best manage this patient’s ascites?

a) Weekly paracenteses with post-procedure albumin replacementb) 2g Sodium and 2L fluid restriction dailyc) 2g Sodium restriction, Spironolactone 100 mg daily and Lasix 40

mg dailyd) Palliative care consult because he’s lucky to be alive





flowAlbumin

Spironolactone

MAP Midodrine

Loop diuretics



Hepatology 2013; 1-27


• Urine sodium • Use spot urine sodium/potassium ratio

• If ratio is >1, pt should be able to lose fluid• The greater the ratio, the greater the sodium excretion

• 24 hour urine collection• Cumbersome and difficult to interpret• Goal is for urine Na >78 mmol/day

• Non-urinary Na loss is <10 mmol/day• Diuretics should be held if urine sodium <30 mmol/day

• Marker of decreased ECF



• Unresponsive to Na restriction and high-dose diuretics (Spironolactone 400 mg/Lasix 160 mg daily)

• Recurs rapidly after paracentesis

• Diuretic failure:• Minimal fluid loss with low urine sodium excretion on

diuretics• Development of complications of diuretics

• Encephalopathy, Cr >2.0, Na <120 mmol/L, K >6.0• Trials show <10% are refractory to optimal therapy (if

adherent)



• Serial Paracenteses• Ascites should be able to be controlled with q2 week Rx• Paracentesis >10 L every 2 weeks suggestive of diet non-

adherence• Albumin administration

• Meta-analysis 1225 patients • Reduction in mortality OR 0.64 (95% CI, 0.41-0.98) in the albumin

group.• Albumin dose: 6-8 g/L of volume removed

• 5% Albumin has 5x the sodium of 25% Albumin



• √ The Learner will explain the evaluation and management of hepatorenal syndrome.

• √ The Learner will apply objective data when managing ascites due to decompensated cirrhosis.


Northern Utah Kidney SpecialistsUniversity of Utah

Department of MedicineDivision of Nephrology and Hypertension


Monique Cho, MDUofU Divison of Nephrology and

Hypertension

Juan Gallegos-Orozco, MD

UofU Transplant Hepatology

Harry Senekjian, MD


Bruce Horowitz, MD


Marcellus Assiago, MD


Northern Utah Kidney SpecialistsUniversity of Utah

Department of MedicineDivision of Nephrology and Hypertension


Trevor R. Smith, MD Northern Utah Kidney Specialists University … · 2019-05-07 · Trevor R....

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