Topic Discussion: Osmotic Nephrosis

Osmotic nephrosis describes a morphological pattern with vacuolization and swelling of the renal proximal tubular cells.

What does the pathology show:

Usually there is acute tubular necrosis–like changes. Histologically, osmotic nephrosis is characterized by a focal or, less often, diffuse “clear-cell” transformation of proximal tubular epithelial cells showing isometric fine vacuolization of the cytoplasm . The straight part of the proximal tubule primarily is involved and, in severe cases, also the convoluted part. Severely affected tubules are often seen side by side with normal-appearing tubules. Distal tubules and collecting ducts are more or less unchanged

Classic known causes of this entity are:

Intravenous immune globulin preparation(sucrose based)

Mannitol Dextrans
Contrast media
Hydroxyethyl starch
Glucose

How does one differentiate this from vacuolization seen with tacrolimus and cyclosporine? Is that a form of osmotic nephrosis?

Renal Pathologist Dr Lynn Cornell nicely describes this on twitter with these images. The image below shows isometric vacuolization in CNI toxicity. This leads to have focal tubules with this change( see arrow)

In osmotic nephrosis, tends to show vacuolated cytoplasm in tubules diffusely( see below)

Osmotic nephrosis describes a morphological pattern with vacuolization and swelling of the renal proximal tubular cells.

In addition, In paraffin sections, the isometric vacuolization seen in patients with calcineurin-inhibitor toxicity may be indistinguishable from osmotic nephrosis. However, electron microscopy shows dilated endoplasmatic reticulum as the cause of vacuolization in the former.  Osmotic nephrosis cannot be differentiated from lipid storage in tubular cells (foam cells), as seen in patients with nephrotic syndrome, liver failure, or intoxication. In such cases, foam cells also are often found in large amounts in the interstitial space. This does not occur in osmotic nephrosis.

The above image shows  osmotic nephrosis in a kidney biopsy specimen. (A, B) Tubular cross-section with seemingly no lumen. Epithelial cells are massively swollen, cytoplasm is completely filled by vacuoles of about the same size (isometric vacuoles), and nuclei are displaced to the base of the cells and distorted by adjacent vacuoles( source https://www.ajkd.org/article/S0272-6386(07)01592-2/pdf

IN THE NEWS: Hydroxyethyl Starch and Ringer's battle it out in NEJM

Hydroxyethyl starch(HES) has been used for volume resuscitation.  It is amylopectin+ hydroxyethyl groups in 0.9% saline or LR.  40-64% of it is excreted by the kidneys.  It is reabsorbed via pinocytosis and no enzymes exist to metabolize the intracellular substances and this leads to accumulation of cellular water and osmotic damage. This can also be seen in IV sucrose or dextran induced injury. This is similar to some forms of IVIG induced injury. Risk factors associated with renal injury have been described as prior CKD, DM, old age, large HES volumes>1 liter.  We as nephrologists have always been skeptical of this agent as its association with osmotic nephrosis.  The first case evert described of osmotic nephrosis with HES was in a kidney transplant patient. A recent NEJM publication looked at a multi centered, blinded trial that randomly assigned patients with severe sepsis to either 6% HES or LR at a dose of 33ml/kg of IBW per day.  The outcome was death and dependence of dialysis. The results showed a significant increased risk of death or dependence of dialysis at 90 days in HES group compared to LR.   The VISEP study had observed similar results but had lower power than this study. This study was randomized and also was international and included university and non university settings. A cochrane review done on this topic prior to this study was not conclusive.  In that meta analysis of 34 studies, it showed that HES had adverse kidney effects mainly in septic patients versus non septic patients. Long terms toxic effects of HES can be seen not only in kidney but in other organs such as bone marrow and liver as well.

After these trials:- probably should be avoided especially in high risk group.
Take a look at a prior post on this topic. 
Check out the article in NEJM.
Some articles that might shed some light on the damage done on cells by HES are presented here
http://www.anesthesia-analgesia.org/content/110/2/300.full
http://www.ncbi.nlm.nih.gov/pubmed/12811231