How common is renal dysfunction in children with liver disease ?



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How common is renal dysfunction in children with liver disease ?

  • How common is renal dysfunction in children with liver disease ?

  • Is every renal dysfunction in liver disease Hepatorenal Syndrome (HRS) ?

  • What is the impact of kidney dysfunction in children with existing liver disease? – Prognosis

  • What is HRS – Definition, pathogenesis, diagnosis

  • Impact of HRS on transplant candidacy?



No data exists in paediatric literature

  • No data exists in paediatric literature

  • Adult data extrapolated.











Extra-hepatic organ dysfunction progresses

  • Extra-hepatic organ dysfunction progresses

  • Common ITU Scores – PIM2, Child Pugh Score, MELD, SOFA, APACHE

  • Renal Dysfunction omitted or only based on SCr

  • How important is the contribution of renal dysfunction to the mortality of patients with liver disease?

  • Inclusion of SCr in Model for End-Stage Liver Disease (MELD)





Is every AKI in liver disease HRS ?

  • Is every AKI in liver disease HRS ?

  • What are the different causes of AKI in liver disease?

  • Can we reliably differentiate between the various causes of AKI?

  • If HRS exists, what is it, clinical manifestations and diagnosis and how do we treat it?

  • Impact of AKI on transplant candidacy?



Pre-renal : Hypovolaemia: GI bleeding – (don’t forget the ulcer ) GI fluid losses (Lactulose, Terlipressin, PPI) Diuretics abuse/over use

  • Pre-renal : Hypovolaemia: GI bleeding – (don’t forget the ulcer ) GI fluid losses (Lactulose, Terlipressin, PPI) Diuretics abuse/over use

  • Acute Tubular necrosis

  • Parenchymal disease: GN, Cryoglobulinaemia, IgA nephropathy – Biopsy? ATN/HRS

  • Drugs: CIN, NSAIDS, Abx, CNI post Tx

  • Intra Abdominal Hypertension

  • Hepato-renal Syndrome



Natural Progression of disease complications Renal dysfunction HRS

  • Natural Progression of disease complications Renal dysfunction HRS

  • V/s

  • Stable patient with cirrhosis, PHT precipitating event HRS





50% of patients with cirrhosis with ascites will develop AKI

  • 50% of patients with cirrhosis with ascites will develop AKI

  • HRS constitutes a very small proportion of AKI in cirrhosis

  • ONLY 7.6% of all 129 cirrhotics with AKI had HRS as the cause of deterioration

  • (Montoliu S, Ballesté B, Planas R, et al )

  • Multicentre trial – 423 patients with cirrhosis and AKI

  • (ATN -35%, Pre-renal failure-32%, HRS-1- 20%, HRS-2 -6.6%

  • (Moreau R, Durand F, Poynard T, et al)



Biliary atresia most common cause of OLT

  • Biliary atresia most common cause of OLT

  • Fewer numbers and split liver transplant

  • Waiting lists smaller – transplant – no HRS

  • Adults – more in number, varied aetiologies, longer waiting lists and develop all complications including HRS

  • HRS in Paediatrics VERY RARE.



  • Hepatorenal syndrome (HRS) is defined as the occurrence of renal failure in a patient with advanced liver disease in the absence of an identifiable cause of renal failure

  • DIAGNOSIS OF EXCLUSION





Bilirubin interferes with assays, with hyperbilirubinaemia masking increase in SCr

  • Bilirubin interferes with assays, with hyperbilirubinaemia masking increase in SCr

  • Ethnic and Sex predilection

  • Liver synthetic function -production of creatinine is reduced by 50%

  • Muscle mass and protein malnutrition

  • Lower baseline range for creatinine in advanced liver disease

  • Cirrhotic patients for a given change in GFR have smaller and delayed changes in SCr

  • Delay access to timely HRS treatment and may adversely affect these patients’ prognosis.









Nitric Oxide (shear-stress-induced upregulation of endothelial NO synthase (eNOS) activity and endotoxin-mediated eNOS)

  • Nitric Oxide (shear-stress-induced upregulation of endothelial NO synthase (eNOS) activity and endotoxin-mediated eNOS)

  • Calcitonin gene-related peptide (CGRP)

  • Substance P

  • Carbon monoxide

  • Endocannabinoids

  • Overproduction of TNF-α may be a major mechanism leading to HRS























Lead to rapid deterioration of the systemic circulation and to the development of the HRS

  • Lead to rapid deterioration of the systemic circulation and to the development of the HRS

  • Gastrointestinal bleeding

  • Spontaneous bacterial peritonitis

  • Sepsis

  • Aggressive diuresis

  • Large volume Paracentesis

  • Cholestasis

  • NSAIDs





  • Hepatorenal syndrome (HRS) is defined as the occurrence of renal failure in a patient with advanced liver disease in the absence of an identifiable cause of renal failure

  • The diagnosis of HRS is one of exclusion, so investigations should be performed to rule out other common causes of AKI.



HRS and ATN difficult to differentiate

  • HRS and ATN difficult to differentiate

  • Granular casts observed in the urinary sediment in both conditions

  • Presence of renal tubular epithelial cells favours ATN

  • FeNa < 1.0% - tubular reabsorptive integrity favours HRS

  • Hpovolemic or septic shock immediately before renal failure - ATN

  • Prolonged HRS ----- ATN ????



Depends on etiology

  • Depends on etiology

  • HRS carries the worst survival among all causes of AKI in cirrhotic patients

  • 562 cirrhotic patients with AKI

  • 3-month survival :

    • HRS patients -15%
    • Infection induced AKI - 31%
    • Hypovolemia-induced AKI -46%
    • AKI associated with evidence of parenchymal renal disease - 73%
  • Determining the etiology of AKI in cirrhotic patients does not only determine the treatment plan but also foretells the prognosis.





Patients with cirrhosis and renal failure are at high risk for death while awaiting transplantation

  • Patients with cirrhosis and renal failure are at high risk for death while awaiting transplantation

  • HRS is a strong predictor of mortality

  • In patients listed for transplantation, the development of HRS – Untransplantable or who receive a transplant associated with increased morbidity and mortality after transplantation



Initially histological abnormalities are minimal and inconsistent

  • Initially histological abnormalities are minimal and inconsistent

  • Tubular function and sodium absorption remains intact

  • Kidneys transplanted from patients with HRS can resume normal function in the recipient

  • Renal function can return in patients with HRS who receive liver transplant

  • Only 2/3rds recover kidney function after transplantation.





Gines et al – 134 HRS patients

  • Gines et al – 134 HRS patients

  • 2-week mortality rate 80% in untreated type 1 HRS patients with only 10% of patients surviving for 3 months

  • Salerno et al - 116 HRS patients

  • Some of them did receive vasoconstrictor therapy

  • 3-month survival was 20% and 40% for type 1 and type 2 HRS, respectively.



AKI common in decompensated cirrhotics

  • AKI common in decompensated cirrhotics

  • Not every AKI in cirrhosis is HRS

  • Extremely rare in paediatrics

  • AKI predicts increased mortality in liver disease

  • HRS drastic complication and carries a very bad prognosis

  • Splanchnic vasodilatation and renal vasoconstriction – main causes

  • Need to know what caused AKI – is it HRS ????



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