Presentation on theme: "Ascites in the chronic renal failure patient with cirrhosis Dr.Rajeev Jayadevan MD (Vellore), DNB (Medicine), MRCP(UK), American Board Certification in."— Presentation transcript:
Ascites in the chronic renal failure patient with cirrhosis Dr.Rajeev Jayadevan MD (Vellore), DNB (Medicine), MRCP(UK), American Board Certification in Medicine American Board Certification in Gastroenterology Senior Consultant Gastroenterologist Sunrise Hospital
Acknowledgements 1.Dr. Jayant Thomas Mathew MD, DM Consultant Nephrologist, Amala Medical College 2.Dr. Sooraj Y.S. MD, DNB (Nephrology) Consultant Nephrologist, Sunrise Hospital 3.Dr. Abi Abraham MD, DM Consultant Nephrologist, Lakeshore Hospital
Outline Refresh our basic physiology about ascites and discuss what is pertinent here Practical aspects of treating a patient with CRF and CLD who has ascites
Ascites in CLD: some basic science A major issue here is that kidneys retain Na and H2O excessively. Why? When kidneys of cirrhotic or heart failure patients were transplanted, they stopped retaining Na and H2O. This meant that the signal for Na/H2O retention came from outside the kidney.
What triggered Na/H2O retention? Could it be low total blood volume? No, because when measured, these patients had normal or, even increased blood volume! Could it be low cardiac output? No, because, pregnancy has high output, but the kidneys still retain Na and H2O!
“Arterial underfilling.” Can be from : 1.Decreased cardiac output 2.Arterial vasodilatation
Estimates of blood volume distribution indicate that 85% of blood circulates on the low-pressure, venous side of the circulation, whereas an estimated 15% of blood is circulating in the high-pressure, arterial circulation. Schrier, J Am Soc Nephrol 18: 2028–2031, 2007 Effective vs. Total blood volume
How does cirrhosis lead to arterial underfilling?
How to treat nephrogenic ascites Patient with ascites, CLD and CRF. Question: Is the ascites from the liver or the kidney?
How to differentiate cirrhotic vs. uremic ascites Cirrhotic Transudate Low protein High SAAG > 1.1 Creatinine < 5 Slow reaccumulation Uremic Exudate High protein Low SAAG Creatinine > 5 Rapid reaccumulation
Ascites in CKD + CLD. Why is treatment difficult? Management difficult as: 1.Symptoms overlap 2.Creatinine value unreliable due to CLD 3.Diuretics don’t work as easily as in CLD: “Diuretic Resistance”
Mechanisms of diuretic resistance in CRF 1. Reduced basal level of fractional Na reabsorption 2. Enhanced NaCl reabsorption in downstream segments: DCT hypertrophy: beyond the reach of Furosemide 3. Reduced delivery of diuretic to the kidney. Diuretics are secreted by the organic anion transporters (OATS), in the PCT, these get inhibited by Acidosis. 4. Hypoalbuminemia decreases delivery of Furosemide and also increases its metabolism to glucuronide
Hypertrophy of distal tubule 1.Taller cells 2.Larger rounded nuclei 3.Taller lateral cell processes Exposure to loop diuretic DCT
Na Due to prolonged action of Loop diuretic in the Loop of Henle, more Na gets absorbed by a hypertrophied DCT
Loop diuretic resistance: Curve shifts to the right DOSE EFFECT
Luminal action NEPHROTIC SYNDROME = ALBUMIN IN LUMEN
Measures to combat diuretic resistance in CRF 1.Restriction of fluid intake 1.5 L daily 2.Maintain Sodium intake of 2 g daily 3.Use of escalating doses of loop diuretics up to established ceiling levels. 4.Judicious use of a second diuretic acting at a downstream site, but watch for ADR 5.Reducing renal proteinuria in nephrotic syndrome using ACEI or ARB J Am Soc Nephrol 13: 798–805, 2002
Diuretic resistance: How to test? If < 50 mmol urine sodium in 8 hours after Lasix 80 mg IV: Resistant. HEPATOLOGY, Vol. 49, No. 6, 2009
Choice of loop diuretic: LASIX vs. TORASEMIDE Preferred Better bioavailability Predictable outcome OD dosing Does better than Lasix in the 6-24 hr interval 20mg as good as 80 mg Lasix
Choice of diuretic- 2 Spironolactone Be cautious Monitor K more closely Patients already on ACEI or ARB, chance of spike in K
What if gynaecomastia? Try Amiloride 10-40 mg/d. Less effective, however.
Second-line agents Triamterene, HCTZ, Metolazone (2.5 - 5 mg OD) are second-line agents used to treat ascites.
Choice of Fluids Be careful with saline: pulmonary edema Albumin/ Plasma are OK: they stay in the intravascular space
Protein in diet: how much? In CKD not on dialysis: very conservative. 0.6-0.8 g/kg/day If on dialysis: can give more: 1.2 g /kg/day
Dialysis patient: what day to tap? Tap on non-dialysis days Heparin can cause bleed otherwise
Dialysis patient with ascites: how to tap: Large-volume paracentesis with IV Albumin replacement at 8 g Albumin per liter of ascitic fluid removed
FFP or Platelets before a tap…..?? No. Routine tests of coagulation do not reflect actual bleeding risk in patients with cirrhosis. These patients regularly have normal global coagulation because of a balanced deficiency of procoagulants and anticoagulants. AASLD guideline HEPATOLOGY, June 2009
Do not send CA-125 in patients with ascites Patients with ascites should not have serum tested for CA-125. It will be elevated due to pressure on mesothelial cells
CKD + Cirrhosis : What dialysis: HD or PD? Peritoneal dialysis: Less hemodynamic instability Less bleed risk Less Hepatitis B/C risk No published increased risk of peritoneal sepsis although theoretical risk from cirrhosis (Same rates of sepsis for CKD patients on PD, regardless of presence of cirrhosis) 40% more expensive
Reinfusion of ascitic fluid into the dialysis machine: PRECEED 2 HD patients with CLD and refractory ascites: quick improvement, well-tolerated
TIPS: any role? Patients with parenchymal renal disease, especially those on dialysis, may not respond as well to TIPS as those with functional renal insufficiency. Michl P, Gulberg V, Bilzer M, Waggershauser T, Reiser M, Gerbes AL. Transjugular intrahepatic portosystemic shunt for cirrhosis and ascites: effects in patients with organic or functional renal failure. Scand J Gastroenterol 2000;35:654-657.
Main points: Ascites in CKD and CLD. 1.Rule out other causes of ascites 2.Diuretic resistance occurs in CKD 3.Furosemide or Torasemide mainstay 4.Use Spironolactone with caution 5.Be liberal with IV albumin 6.Avoid IV fluids like saline 7.Work closely with the nephrologist
Treatment of hepatorenal syndrome Albumin infusion plus administration of vasoactive drugs such as octreotide and midodrine should be considered in the treatment of type I hepatorenal syndrome. (Class IIa, Level B) HEPATOLOGY, June 2009
Major criteria for the diagnosis of hepatorenal syndrome 1.Cirrhosis with ascites 2.Serum creatinine >1.5 mg/dL 3.No improvement with diuretic withdrawal or IV albumin 4.Absence of shock 5.No current or recent treatment with nephrotoxic drugs 6.Absence of parenchymal kidney disease U/A or USG
Dr. Robert W. Schrier “decreased effective blood volume” can be considered outdated and be replaced by “arterial underfilling.”
Sympathetic atrophy In the late stages of portal hypertension. Decreases the vascular tone of the mesenteric tree, allowing an increased activity of vasodilatory mediators
Does Fluid retention lead to ascites? Not necessarily. Many patients with fluid retention have no ascites. Fluid retention per se seen in patients with nephrogenic ascites is unlikely to account solely for ascites formation.
Diuretic resistance: How to test? 8 hour urine excretion of 50 mmol after 80 mg of IV Lasix confirms diuretic sensitivity.
Nephrogenic ascites Nephrogenic ascites is defined as clinically evident chronic ascites, occurring in patients with ESRD without other clear cause. Its pathogenesis remains unknown, has limited treatment options and is associated with a grave prognosis. J. Am. Soc. Nephrol. 1994; 5:1 173-1 177)
Epidemiology Nephrogenic ascites has marked center-to-center variability in incidence (0.7 to 20%) A wide age range of onset ( 1 1 to 71 yr; mean, 42 yr) Male sex (male : female = 2: 1 )
How long before ascites develops? Ascites accumulation can occur as early as 18 months before or as late as 69 months after the initiation of hemodialysis
Possible pathogenesis of nephrogenic ascites Elevated Hepatic Venous Hydrostatic Pressure Volume Overload Increased Peritoneal Membrane Permeability – Secondary to Uremic toxins – Prior exposure to dialysis solutions – Renin-angiotensin activation – Circulating immune complexes deposit on peritonal membrane – Hemosiderosis Impaired Lymphatic Drainage
Mechanisms of diuretic resistance in CRF 1. Reduced basal level of fractional Na reabsorption 2. Enhanced NaCl reabsorption in downstream segments: DCT hypertrophy: beyond the reach of Furosemide 3. Reduced delivery of diuretic to the kidney. Diuretics are actively secreted by the organic anion transporters (OATS), in the PCT, these get inhibited by Acidosis and competition from organic anions. 4. Hypoalbuminemia decreases delivery as loop diuretics are protein-bound of Furosemide and also increases its metabolism to glucuronide
Mechanisms of diuretic resistance in CRF 1. Reduced basal level of fractional Na reabsorption 2. Enhanced NaCl reabsorption in downstream segments: DCT hypertrophy: beyond the reach of Furosemide 3. Reduced delivery of diuretic to the kidney. Diuretics are secreted by the organic anion transporters (OATS), in the PCT, these get inhibited by Acidosis. 4. Hypoalbuminemia decreases delivery of Furosemide and also increases its metabolism to glucuronide 5. Post-diuretic salt retention
Spironolactone Stops the Na- retaining action of Aldosterone on renal collecting tubules May use singly (sequentially) or in combination with Furosemide Use with great caution in renal failure
How to titrate weight loss? There is no limit to the daily weight loss of patients who have massive edema. Once the edema has resolved, 0.5 kg is probably a reasonable daily maximum. Encephalopathy, Na 2.0 mg/dL should lead to reassessment of diuretic regime.
Antibiotic use in SBP: choice and dose 1) Patients with ascitic fluid PMN counts >250 cells/mm3 should receive empiric antibiotic therapy, Cefotaxime 2 g IV Q 8H. (Class I, Level A) 2) Oral Ofloxacin 400 mg bd considered a substitute for intravenous cefotaxime in inpatients without complications
Antibiotic use in ascites of CLD Oral Norfloxacin 400 mg daily to be considered long-term Watch for adrenal insufficiency in severe sepsis N Engl J Med 2009;361:1279-90. In patients with cirrhosis and ascites but no gastrointestinal bleeding, long-term use of norfloxacin (or trimethoprim/sulfamethasoxazole) can be justified if the ascitic fluid protein <1.5 g/dL and at least one of the following is present: serum creatinine >1.2 mg/dL, blood urea nitrogen >25 mg/dL, serum sodium 9 points with bilirubin >3 mg/dL. (Class I, Level B)
Dialysis patient developing ascites: when to tap? If dyspnea or severe distention
Dosing….the 100:40 ratio (Spironolactone:Furosemide) The doses of both can be increased simultaneously every 3-5 days (maintaining the ratio). This ratio maintains K+ levels if normal kidneys Maximum doses are 400 mg/day and 160 mg/day
Exudative ascites (Serum Albumin - Ascites Albumin <1.1 gm/dl) Neoplastic diseases involving the peritoneum: Peritoneal carcinomatosis, Lymphomatous disorders Tuberculous peritonitis Pancreatitis Post surgery talc or starch powder peritonitis Transected lymphatics following portal caval shunt surgery Myxedema Sarcoidosis Lymphatic obstruction: a. Intestinal lymphangiectasia, b. Lymphoma Pseudomyxoma peritonei Struma oovarii Amyloidosis Prior abdominal trauma with ruptured lymphatics Hemodialysis CRF related ascites
Transudative ascites (SAAG >1.1 gm/dl) Liver cirrhosis Congestive heart failure Hepatic vein obstruction (Budd Chiari syndrome) a. Assoc. with tumors (hepatoma, hypernephroma, pancreatic Ca) b. Assoc. with hematologic disorders (myeloproliferative disease, polycythemia vera, myeloid metaplasia c. Due to infections Nephrotic syndrome Meig's ovarian tumor syndrome Constrictive pericarditis Inferior vena cava obstruction Viral hepatitis with submassive or massive hepatic necrosis
Uremic encephalopathy Can precipitate due to volume shift at paracentesis Avoid by using albumin cover
Diuretic resistance: How to test? A random “spot” urine sodium concentration that is greater than the potassium concentration correlates with a 24-hour sodium excretion greater than 78 mmol/day with approximately 90% accuracy. Stiehm AJ, Mendler MH, Runyon BA. Detection of diuretic-resistance or diuretic-sensitivity by the spot urine Na/K ratio in 729 specimens from cirrhotics with ascites: approximately 90% accuracy as compared to 24-hr urine Na excretion. HEPATOLOGY 2002;36:222A.