Osmotic Tubulopathy



Osmotic Tubulopathy


Shane M. Meehan, MBBCh










Osmotic tubulopathy in a kidney transplant due to IVIg exposure shows that there is proximal tubular epithelial swelling, luminal obliteration, and vacuolar change. The glomerulus appears shrunken image.






Osmotic tubulopathy in a kidney transplant due to IVIg exposure shows vacuolar changes that are evident in pars recta and pars convoluta, with sparing of collecting ducts image and loops of Henle image.


TERMINOLOGY


Abbreviations



  • Osmotic tubulopathy (OT)


Synonyms



  • Osmotic nephrosis, contrast nephropathy, (radio)contrast-induced acute kidney injury, intravenous immunoglobulin-associated tubular toxicity


Definitions



  • Tubular epithelial swelling and isometric vacuolization, associated with exposure to parenteral carbohydrate solutions or contrast media, and acute kidney injury


ETIOLOGY/PATHOGENESIS


Causes



  • Parenteral infusion of hyperosmolar agents including



    • Parenteral carbohydrate solutions



      • Mannitol: Used as plasma expander and for treatment of cerebral edema


      • Dextran: Used as plasma expander


      • Hydroxyethyl starch (HES): Used as plasma expander and in perfusion preservation of kidney transplants (UW solution)


      • Glucose, sucrose, and maltose: Stabilizing agents


    • Intravenous immunoglobulin (IVIg): Sucrose and maltose used as stabilizing agents


    • Radiologic contrast agents: Iodine-containing agents, ionic or nonionic, high and low osmolality


Pathogenesis



  • Hyperosmotic solutions are filtered and then absorbed by proximal tubules by pinocytosis


  • Solute is retained in endosomes and not broken down


  • Intracellular oncotic gradient is thus created and results in water absorption and hydropic swelling


  • Accumulation of pinocytotic vesicles is dose related


  • Vacuoles arise by fusion of vesicles with lysosomes


  • Experimentally, vacuolar change appears in minutes and disappears in days after exposure


  • Direct toxicity from disruption of cellular integrity and possible oxidative injury


  • Secondary afferent arteriolar vasoconstriction and efferent vasodilation reduces glomerular filtration rate


Risk Factors



  • Age > 65 years


  • Preexisting chronic renal failure and diabetic nephropathy


  • Concurrent exposure to nephrotoxic agents


  • Coexistent ischemic or hypoxic renal injury, especially in kidney transplants


  • Dehydration


  • Quantity and osmolarity of administered solution, especially for contrast media and mannitol


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Incidence varies with agent administered and presence of associated risk factors


Presentation



  • Acute deterioration of function of native and transplanted kidneys with exposure to inciting agents


  • Renal failure may develop and resolve without clinical symptoms or signs


  • Renal failure is typically oliguric


  • Renal dysfunction begins within days of infusion and reverses after cessation of infusion


  • Persistent impairment is rare


  • High osmolal gap (measured osmolality minus calculated osmolality)


  • Diagnosis is by kidney biopsy



Treatment



  • Prevention by hydration using iso-osmolar fluids


  • Renal replacement therapy necessary in up to 40% of patients


  • Plasma exchange for removal of dextran


Prognosis



  • Recovery after cessation typically takes days to weeks


  • Prolonged renal failure over months may be observed


  • End-stage renal failure is rare


  • Significant increase in mortality associated with acute renal failure


MACROSCOPIC FEATURES


Gross Examination



  • Enlarged and pale kidneys


MICROSCOPIC PATHOLOGY


Histologic Features

Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Osmotic Tubulopathy
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