Thursday, March 24, 2011

Is peritoneal dialysis a viable option in patients with cirrhosis and ascites ?


Theoretical disadvantages of PD when compared to HD?
1. Increased risk of peritonitis.
2. Ongoing and higher protein losses in dialysate may aggravate malnutrition. And, with excessive protein supplementation there may be worsening of hepatic encephalopathy.
3. More hypokalemia – can worsen encephalopathy by increasing ammonia production in PT and also results in impaired motility of the gut -> increased bacterial colonization and peritonitis risk.
4. Intrabdominal bleeding from catheter trauma.
5. Might adversely affects transplantation rates or increase peri-transplant morbidity secondary to adehesions, etc.

Theoretical advantages of PD when compared to HD?

1. Avoids hypotension episodes and better preserves residual renal function.
2. Rapid drop in plasma osmolality with HD can results in cerebral edema and AMS.
3. Dialysate can serve as source of calories in malnourished patients.
4. Avoids risk of bleeding with cannulation that is associated with HD.
5. Increased intra-abdominal pressure opposes portal & splanchnic hypertension and less formation & accumulation of ascites.
6. Ultrafiltration capacity augmented with respect to non-cirrhotic patients (as ascites is removed) – making use of hypertonic bags unnecessary.
7. PD removes endotoxins (part of GNB cell walls) and Nitric Oxide in the ascitic fluid.
8. Peritonitis is detected much earlier & non-invasively as cloudiness of the fluid is readily noticeable.

*Pertitonitis rates reported in literature are varied and inconclusive:
Chow et al (Hongkong):
Compared 25 patients with HBV with cirrhosis on PD vs. 36 HBV patients without cirrhosis on PD.
Mean follow-up: 4 years
Peritonitis rate: 1 episode/19.2 months in cirrhotics vs. 1/20.5 months in non-cirrhotics (NS).
No difference in time to first peritonitis between groups.
None of the patients were on antibiotic prophylaxis.
Significant increase in alpha hemolytic strep infections.
No increase in enterobacteriacea peritonitis.

*DeVecchi et al (Italy):
Compared 21 cirrhotics on PD vs. 41 non-cirrhotic PD patients.
Mean follow-: 3 years
Peritonitis rate lower in cirrhotic group. 1/39 months vs. 1/22 months.
Unclear whether pateints were on antibiotic prophylaxis.

*Selgas et al (Spain):
Case series with 8 cirrhotics.
Peritonitis rate: 1 episode/9 months (2.5x higher than their average rate).
Unclear whether patients were on antibiotic prophylaxis.
Peritonitis due to S. faecalis, E.coli and gram negative bacilli significantly higher.

Suggested management strategies for PD in patients with ascites:
*At PD initiation:
A. Initial large volume paracentecis thorugh newly placed PD catheter with IV albumin support for hemodynamic stability to alleviate pressure at suture site and promote healing of catheter site and reduces chances of a leak.
B. Initial PD regimen should be low-volume supine regimen with no ambulatory dialysis – to reduce chance of leak.
C. Controlled paracentecis/drain restricted exchanges (limit to 2400-2500 ml/drain) with low dextrose concentration: Allows for eventual slow removal of ascites.

*Ongoing stratergies:

A. Prevention & treatment of peritonitis episodes.

1. Consider oral prophylactic antibiotics for SBP.
2. Topical gentamycin ointment for exit site care.
3. Chronic lactulose therapy – metabolized by colonic bacteria into pyruvate and lactate which acidify the stool and reduce bacterial colonization.
4. Avoid hypokalemia – can worsen intestinal motility and bacterial overgrowth.
5. PD itself, by removing endotoxins (component of GNB cell walls) and Nitric Oxide in the ascitc fluid, may reduce inflammation fo the peritoneal membrance. It can also reduce portal pressure gradient and reduce bleeding from varices.
6. Intraperitoneal antibiotics effective.
7. Initial regimen should provide broad spectrum coverage and include ampicillin.
8. Rx with intraperitoneal antibiotics + IV albumin reduced morbidity, mortality rate and prevented subsequent deterioration of renal function in one study. In addition to providing colloidal osmotic pressure, albumin also binds cytokines produced during peritonitis.

B. Protein losses in dialysate.

1. Several studies have shown that peritoneal protein losses are high initially but diminish over time. Monitor nutritional parameters closely.
2. Non-restricted diet is recommended
3. Oral protein supplements as needed.

C. Transplantation rates.

1. None of the large studies list transplantation rates.

References:
1. Chow et al. Peritoneal Dialysis International, Vol. 26, pp. 213–217.
2. DeVecchi et al. American Journal of Kidney Diseases, Vol 40, No 1 (July), 2002: pp 161-168.
3. Steven Guest. Advances in Peritoneal Dialysis, Vol. 26, 2010
3. Selgas et al. Peritoneal Dialysis International, Vol. 28, pp. 118–122.

Publication alert: HIV-associated nephropathy: pathogenesis.

AUTHORS:
Raj Kiran Medapalli, MD, MPH, John Ci-jiang He, MD, PhD and Paul E. Klotman, MD.

REFERENCE:
Curr Opin Nephrol Hypertens. 2011 Feb 23. [Epub ahead of print]

ABSTRACT:
PURPOSE OF REVIEW: HIV-associated nephropathy (HIVAN) is characterized histologically by a collapsing form of focal segmental glomerulosclerosis (FSGS), microcystic tubular dilation, interstitial inflammation and fibrosis. In this review, we provide a summary of the current state of knowledge about the mechanisms involved in the pathogenesis of HIVAN.
RECENT FINDINGS: Two variants in the ApoL1 gene have been identified as the susceptibility alleles that account for a majority of the increased risk of FSGS and nondiabetic end-stage renal disease in blacks. HIVAN1 and HIVAN2 are the other host susceptibility genes that have been identified in animal models for HIVAN. HIV infects renal tubular epithelial cells likely through direct cell-cell transmission. Both in-vivo and in-vitro evidence suggests that Nef and Vpr are the key viral genes mediating HIVAN. Nef induces podocyte dysfunction, whereas Vpr induces renal tubular epithelial cell apoptosis.
SUMMARY: HIVAN results from direct infection by HIV-1 and expression of viral genes, especially Nef and Vpr, in renal epithelial cells in a genetically susceptible host. The infected renal epithelium acts as a separate viral compartment from the blood and facilitates evolution of strains distant from blood. Dysregulation of several host cellular pathways, including those involved in cell cycle and apoptosis, ultimately results in the unique histopathological syndrome of HIVAN.

Publication alert: Expert opinion on pharmacotherapy of kidney disease in HIV-infected patients.

Authors:
Zygimantas C. Alsauskas, MD, Raj Kiran Medapalli, MD, MPH, Michael J. Ross, MD.

Reference:
Expert Opin Pharmacother. 2011 Apr;12(5):691-704. Epub 2011 Jan 21.

Abstract:
Introduction: Human immunodeficiency virus (HIV) infection is associated with the development of a wide spectrum of kidney diseases. HIV-associated nephropathy (HIVAN) is the most common cause of chronic kidney disease (CKD) in HIV-infected individuals and predominantly affects patients of African ancestry. HIVAN is a leading cause of end-stage renal disease (ESRD) among African-Americans. Areas covered: An overview of the spectrum of kidney disease in patients with HIV is given. Current pharmacologic interventions to treat kidney disease in HIV are discussed. This review will enhance knowledge regarding the most common causes of kidney disease in HIV-infected patients. An understanding of the principles related to pharmacotherapy in HIV-infected patients with kidney disease will also be gained.
Expert opinion: Kidney disease is an important cause of morbidity and mortality in HIV-infected patients. The most common cause of chronic kidney disease in this population is HIV-associated nephropathy, which is caused by viral infection of the renal epithelium. Several medications that are commonly used in HIV-infected patients can have adverse effects on the kidneys and the doses of many antiretroviral medications need to be adjusted in patients with impaired renal function.

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