Renal Support in Hepatic Patient

1. Renal Support in Hepatic Patient By Mohammed Dabbour Lecturer of Anesthesia Ain shams University

2. Outline Introduction Definition Epidemiology Pathophysiology Precipitating factors Diagnosis Management (Prevention and treatment) Conclusion

3. Introduction Renal dysfunction is a common and serious problem in patients with advanced liver disease. In particular, alterations in renal physiology in acute liver failure or cirrhosis with ascites can predispose patients to a specific functional form of renal failure known as hepatorenal syndrome The accurate assessment of the kidney function and injury is currently affected by the reliance on the measured concentration of serum creatinine,which is significantly affected by the degree of cirrhosis, hyperbilirubinemia and the nutritional state of the patient.

4. Epidemiology The predictive factors for the development of HRS include: - a low serum sodium - high plasma rennin - absence of hepatomegaly

5. Co-existing liver and kidney disease ■ Chronic liver disease and primary liver cancer ■ Obesity and metabolic syndrome are also strongly associated with the development of hypertension and diabetes ■ Hepatitis C has long been associated with several glomerulopathies Viral RNA, proteins and particles have been isolated from kidney biopsy specimen, hepatitis C infection has been reported to be associated with focal segmental glomerulosclerosis. Hepatitis C also has been associated with an increased risk of albuminuria, progression of diabetic nephropathy and progression of kidney disease.

6. ■ Hepatitis B virus (HBV) is associated with a number of renal disease, including polyarteritisnodosa, membranous and membranoproliferativeglomerulonephritis ■Autosomal-dominant polycystic kidney is associated with polycystic liver disease in up to 75-90% of cases ■ Familial amyloidosis is an autosomal dominant disease

7. Renal diseases associated with major types of liver disease

8. Systemic diseases involving both liver and kidney

9. Serum creatinine concentration for the assessment of kidney function in chronic liver disease Kidney function is evaluated by assessing the GFR which can be determined by measuring the volume of plasma that can be cleared of a given substance over a timed unit of time GFR has relied on the measurement of the concentration of serum creatinine, which is associated with many problems: - specific, but not sensitive - measurement is affected by gender, age, ethnicity, nutritional state, protein intake and importantly, liver disease In chronic liver disease, the reduction in serum creatinine is due to a 50% decrease in hepatic production of creatinine and increase in the volume distribution

10. Acute Kidney Injury Network Criteria for staging Acute Kidney Injury In 2005, the Acute Kidney Injury Network (AKIN) developed the RIFLE(Risk, Injury, Failure, Loss, End stage renal disease) criteria

11. Acute kidney injury network(AKIN)acute kidney injury staging criteria

12. Acute Kidney Injury Pathogenesis A. Isolated ischemic injury → Inflammatory response →Leucocyte release & tubular damage → impaired Na reabsorption→ polymerization of Tamm-Horsfall proteins → gel-like substance formation → tubular occlusion → increased backpressure & leaking B. Endothelial injury → affects afferent arteriolar tonicity → clotting cascade activation & endothelin release → VC → compromising the microcirculation

13. Bacterial infection Large volume paracentesis Acute alcoholic hepatitis GItbleeding Renal vasoconstriction Worsening hyperdynamic circulation Cardiac dysfunction ((septic or cirrhotic Renal Vasoconstrictor ↑ Renal Vasodilator ↓

14. Biomarkers of AKI • Traditional markers: • Serum creatinine • Serum urea • Urine markers • Fractional excretion of sodium • Urine casts on microscopy • Novel kidney biomarkers:Two serum and three urine biomarkers • Serum neutrophilgelatinaseLipocalin (sNGAL) • Cystatin C • Urinary Kidney Injury Molecule (KIM-1) • Interleukin-18 (IL-18) • NGAL (uNGAL)

15. Summary of studies evaluating the role of novel blood and urine kidney injury biomarkers `

16. Precipitating Factors Spontaneous bacterial peritonitis Gastrointestinal bleeding Aggressive paracentesis Drugs Others

17. Spontaneous Bacterial Peritonitis Renal impairment is related to further deterioration of systemic hemodynamics, mostly by endotoxins and various cytokines induced in SBP, causing further vasodilatation Gastrointestinal bleeding Acute gastrointestinal bleeding leads to acute blood volume contraction, with decreased renal perfusion

18. Aggressive paracentesis • It reduces the effective arterial blood volume and further activates vasoconstrictor system Drugs • Diuretics • Aminoglycosides • Nonsteroidal anti-inflammatory drugs • ACE-inhibitors • Angiotensin II antagonists Others: - Surgery, acute alcoholic hepatitis and cholestasis

19. Definition of HRS HRS is defined as the development of renal failure in patients with advanced liver failure (acute or chronic) in the absence of any identifiable causes of renal pathology In 1996, the International Ascites Club subdivided HRS into 2 types;

20. Hepatorenal syndrome Type I Type II ■ renal function deteriorates more slowly ■ serum creatinine increases to > 1.5 mg/dL or a creatinine clearance of < 40 mL/min. ■ The clinical presentation is that of stable renal failure in a patient with refractory ascites • ■characterized by a rapid decline in renal function • ■ defined as a doubling of serum creatinine to a level > 2.5 mg/dL or a halving of the creatinine clearance to < 20 mL/min within 2 weeks • ■ clinical presentation is that of acute renal failure

21. Diagnosis of HRS Some patients with primary liver disease are at higher risk for developing certain forms of kidney disease while some systemic processes can affect both liver and kidney Major criteria should be fulfilled to confirm diagnosis

22. Hepatorenal syndrome: Diagnostic criteria Major criteria (all must be present) Chronic or acute liver disease with advanced hepatic failure and portal hypertension Low GFR as indicated by a 24-hr creatinine clearance of < 40 mL/min or serum creatinine > 1.5 mg/dL Absence of shock, sepsis, volume depletion, exposure to nephrotoxins No sustained improvement in renal function (to creatinine > 1.5 mg/dL or 24-hr CrCl to > 40 mL/min) following diuretic withdrawal or plasma volume expansion with 1.5 L of normal saline Proteinuria < 500 mg/dL No ultrasonographic findings of obstructive uropathy or parenchymal renal disease

23. Additional criteria (not necessary but would support diagnosis) • Urine volume < 500 mL/day • Urine sodium < 10 mEq/L • Urine osmolality greater than plasma osmolality • Urine red blood cells < 50 per high-power field • Serum sodium < 130 mEq/L

24. Work-up for patients with suspected HRS • History • Fluid losses -- vomiting, diarrhea, diuretic use • Gastrointestinal bleeding • Infection -- fever, cough, dysuria, abdominal discomfort • Exposure to nephrotoxins -- drugs (aminoglycosides, NSAIDs), radiocontrast agents • Physical exam • Heart rate, blood pressure (including orthostatic), temperature • Signs of infection (pulmonary, abdominal, cellulitis, etc.) • Other causes of renal failure -- purpuric rash may suggest cryoglobulinemia • Investigations • Complete blood count, electrolytes, creatinine level • Urine sodium, osmolality • Urinalysis for protein, cells, and casts • Renal ultrasound

25. Assessment of Chronic kidney Disease in patients with chronic Liver disease Timed urine creatinine clearance performs poor significance overestimating GFR in patients with chronic liver disease So why use estimated GFR if it performs so poorly ????? Because it is the most cost-effective method of assessing kidney function in chronic cases

26. Staging criteria for chronic kidney disease

27. Management of HRSPrevention & treatment ♣ Prevention: • Prophylaxis against bacterial infection • Volume expansion • Strict use of diuretics • Avoidance of nephrotoxic agents

28. ♣ Treatment: Initial management: It requires exclusion of reversible or treatable conditions Pharmacologic therapy Renal support TransjugularIntrahepaticPortosystemic Shunt Liver transplantation

29. Pharmacologic therapy ● Dopamine Has renal vasodilator effect when given in subpressor doses, but no studies have shown convincing benifit ● Noradrenaline was used with albumin and frusemide in management of patients with type I HRS ● Midodrine & Octreotide Midodrine is an oral alpha adrenergic agent and sympathomimetic drug Octreotide is a long acting analog of somatostatin Combined long term administration of oral midodrine and subcutaneous octreotide lead to improvement in renal function compared with nonpressor doses of dopamine

30. ● Misoprostol It is a synthetic analogue of prostaglandin E1, acts as a renal vasodilator ● Ornipressin It is a nonselective agonist of V1 vasopressin receptors that causes VC of the splanchnic vasculature, thus increasing systemic pressure and renal perfusion pressure ● Terlipressin It is a synthetic analogue of vasopressin with VC activity . Lowers incidence of ischemic complications . Longer half life than vasopressin

31. ● Endothelinanatgonists Enothelin is a potent endogenous vasoconstrictor, so renal failure was prevented by an endothelinanatgonist, e.g., Bosentan ● N-acetylcysteine It is a drug with antioxidant properties ● Pentoxifyllin It inhibits the tumor necrosis factor

32. Renal support Dialysis: The effectiveness of dialysis has not been proven Molecular Adsorbent Recirculating System This system is a modified form of dialysis using albumin-containing dialysate that is recirculated and perfused online through charcoal and anion exchanger columns. It enables the removal of water and albumin bound substances

33. TransjugularIntrahepaticPortosystemic Shunt Liver transplantation Endstage liver and kidney disease is a recognized indication for combined liver-kidney transplant

34. Conclusion Chronic liver disease is associated with primary and secondary kidney disease Evaluation of kidney function relies on the measurement of serum creatinine, which is affected by the degree of liver disease Hepatologists should use exogenous measures of kidney functions & biomarkers like cystatin C Kidney Injury Biomarkers need further evaluation in the chronic liver disease population Early diagnosis potentially increases the survival outcomes

35. Numerous studies have shown the benefit of terlipressin with fewer side effects The combination of midodrine and octreotide can be used in absence of terlipressin Intravenous albumin should be considered. Orthotopic liver transplantation is the most effective strategy for the treatment of hepatorenal syndrome.

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