Human Kidney Histopathology in Obstructive Jaundice

This study has been completed.
Sponsor:
Information provided by:
Turkish Ministry of Health Izmir Teaching Hospital
ClinicalTrials.gov Identifier:
NCT01090193
First received: March 18, 2010
Last updated: NA
Last verified: January 2009
History: No changes posted
  Purpose

Introduction: Cholemia and bacterial translocation with portal endotoxemia are integral in the pathogenesis of obstructive jaundice (OJ). There is sufficient experimental data about hemodynamic and histopathologic consequences of OJ. On the contrary, pathologic information of renal changes in patients with OJ is still lacking. Therefore; the primary objective of this prospective study is to demonstrate the specific histopathologic changes in kidneys of patients with short-term biliary tract obstruction receiving a standard perioperative medical treatment protocol.


Condition Intervention Phase
Patients With Obstructive Jaundice
Procedure: Whipple operation,Hepaticojejunostomy
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Phase 4 Study :Human Kidney Histopathology in Acute Obstructive Jaundice: a Prospective Study

Further study details as provided by Turkish Ministry of Health Izmir Teaching Hospital:

Primary Outcome Measures:
  • Human kidney histopathology in acute obstructive jaundice: a prospective study [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    the primary objective of this prospective study is to demonstrate the specific histopathologic changes in kidney parenchyme of patients undergoing surgery for short-term biliary tract obstruction.


Secondary Outcome Measures:
  • Human kidney histopathology in acute obstructive jaundice: a prospective study [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    The secondary objective is to approve the feasibility of a standard perioperative medical treatment protocol, which has been implemented on a routine basis in our department over the last decade.


Enrollment: 20
Study Start Date: January 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
obstructive jaundice Procedure: Whipple operation,Hepaticojejunostomy
Whipple operation, Hepaticojejunostomy
Other Name: Internal biliary drainage operations

Detailed Description:

Twenty consecutive patients with biliary obstruction were included. Fluid replacement, prevention of biliary sepsis and portal endotoxemia were mainstays of the perioperative treatment protocol. Fluid and electrolyte balance was maintained by twice daily body weight calculations, central venous pressure and mean arterial pressure (MAP) monitoring . Renal function was assessed by glomerular filtration rate estimation via MDRD-7 formula.

Kidney biopsy evaluation was focused on tubular changes, thrombotic microangiopathy, endothelial damage and peritubular capillary (PTC) dilatation with or without C4d staining. Fresh frozen sections were evaluated with immunoflourescence (IF)microscopy for glomerular IgG, IgA, IgM, C3, and C1q staining.

Despite those favourable figures, dilatation of peritubular venules and acute tubular necrosis were demonstrated synchronously in all cases. C4d staining in PTC and arterioles and thrombotic microangiopathy were entirely absent in the study group. Immune complex deposits in peritubular capillaries and in glomeruli were not detected. Three patients had isolated glomerular C4d deposition without accompanying thrombotic microangiopathy and IgG, IgA, IgM, C3, and C1q staining of glomerular capillaries in IF microscopy.

Discussion: This study is the first in the literature to address the histopathologic changes that occur in humans with short-term biliary obstruction. ATN and venous dilatation was observed in all biopsies, without exception, despite the maintenance of strict volume control in all patients. The adequacy of volume control may not be implicated in those results; rather a possible mechanism related to untrapped endotoxin in the gut lumen or systemic circulation might lead to prolonged peritubular capillary dilatation and hypoperfusion with synchronous acute tubular necrosis . Absolute recovery of renal function in all patients and the demonstration of solitary ATN with no microvascular-glomerular-interstitial inflammation or injury, suggests that the perioperative treatment regime in this study is fairly efficacious in short-term OJ.

  Eligibility

Ages Eligible for Study:   26 Years to 86 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Between January 2009 and January 2010, twenty consecutive patients with an equal distribution of biliary obstruction type (10 malignant and 10 benign) were included into the study.

Exclusion Criteria:

  • Patients over 60 years of age or those with a history of co-morbid cardiac disease were initially evaluated by echocardiography.
  • Those with an ejection fraction rate <50% and left ventricular end-diastolic diameter (LVDD) over 52 mm. were excluded from the study because of the already existing left ventricular dysfunction compromising the optimisation of fluid replacement.
  • Patients with a history and serologic evidence of acute/chronic parenchymal kidney or liver disease were also excluded.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01090193

Locations
Turkey
Izmir Teaching Hospital, Department of General Surgery
Izmir, Turkey, 35290
Sponsors and Collaborators
Turkish Ministry of Health Izmir Teaching Hospital
Investigators
Principal Investigator: Adam Uslu, Assoc. Prof. Izmir Teaching Hospital
  More Information

Publications:
Responsible Party: Assoc. Prof. Adam Uslu/ Chief of the Department of General Surgery, Turkish Ministry of Health Izmir Teaching Hospital
ClinicalTrials.gov Identifier: NCT01090193     History of Changes
Other Study ID Numbers: BZYK01
Study First Received: March 18, 2010
Last Updated: March 18, 2010
Health Authority: Turkey: Ethics Committee
Turkey: Ministry of Health

Keywords provided by Turkish Ministry of Health Izmir Teaching Hospital:
Obstructive jaundice
kidney histopathology
lactulose

Additional relevant MeSH terms:
Jaundice
Jaundice, Obstructive
Hyperbilirubinemia
Pathologic Processes
Skin Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on July 23, 2014