Human Kidney Histopathology in Obstructive Jaundice

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 4 Study :Human Kidney Histopathology in Acute Obstructive Jaundice: a Prospective Study

Conditions
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Patients With Obstructive Jaundice

Intervention / Treatment
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* Procedure: Whipple operation,Hepaticojejunostomy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 26 Years
Maximum Age: 86 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: obstructive jaundice<br> | Procedure: Whipple operation,Hepaticojejunostomy<br>* Whipple operation, Hepaticojejunostomy<br>* Other names: Internal biliary drainage operations;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human kidney histopathology in acute obstructive jaundice: a prospective study | 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. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Human kidney histopathology in acute obstructive jaundice: a prospective study | 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. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Obstructive jaundice, kidney histopathology, lactulose