Patients With Obstructive Jaundice Clinical Trial
Official title:
Phase 4 Study :Human Kidney Histopathology in Acute Obstructive Jaundice: a Prospective Study
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.
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.
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Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic