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.



  • Osmotic tubulopathy (OT)


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


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



  • 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


  • 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



  • Incidence

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


  • 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


  • Prevention by hydration using iso-osmolar fluids

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

  • Plasma exchange for removal of dextran


  • 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


Gross Examination

  • Enlarged and pale kidneys


Histologic Features

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

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