Acute interstitial nephritis txt

This is the low-bandwidth, text alternative to the video Acute interstitial nephritis, from the post Interstitial renal diseases.

A short tour through the important causes of acute interstitial nephritis. Remember that unlike glomerular diseases, which are mostly autoimmune, or sometimes immune, for interstitial nephritis the major causes are:

• Allergic
• Infectious
• or Noxious

We’re talking about disease that doesn’t affect the glomeruli, but affects the loops of tubules in between.

 

Allergic (sometimes autoimmune)

On the left is normal kidney, and on the right is something that is very abnormal. Instead of back-to-back tubules, looking very healthy, with an even epithelium and nuclei around them, these are all different sizes, they’re separated by oedema, and by an inflammatory infiltrate, in which even at this low magnification, you can possibly see some of the lymphocytes there are invading the tubules that they are surrounding.

It’s important to say that you can get an interstitial nephritis with a severe glomerulonephritis. And here is an example:

This glomerulus on the right has a focal necrotic segment. And round about is an extensive inflammatory infiltrate. We’re talking today about interstitial inflammatory nephritis not involving the glomeruli.

Here it’s very clear that you can see in many places many little black nuclei invading into tubular outlines. So much so that some of these tubular outlines are being completely obliterated. This is most commonly a reaction to a drug which presumably binds to the tubular cells, creating a new complex antigen (haptenising; forming a neoantigen). And then this complex neoantigen becomes the target of immune attack, by your own immune system. If you were to stop the drug and let it wash out, the immune reaction would die down. But a lot of damage might be done by then.

Typically, but not completely diagnostically, these allergic responses are accompanied by quite a lot of eosinophils in the biopsy. And you can see quite a few here. These very pink cells scattered through the inflammatory infiltrate. The most common culprit drugs are antibiotics, particularly in high doses administered for some time. PPIs, proton pump inhibitors, such as omeprazole, and actually a whole range of other drugs can occasionally do this as well. Non-steroidals are the other big culprit.

Here, helpfully, the tubules have been separated by an enormous amount of oedema. And you can very clearly in this outline scores of lymphocytes invading this poor tubule. This in fact is an example of severe rejection of a kidney transplant . So these are the patient’s immune cells reacting against the donor HLA antigens. This cellular type of rejection can look just about identical to any tubulo-interstitial nephritis.

Here’s a more typical example to omeprazole. So this is a patient with a chronic disease who gets some regular blood tests, so you can see on the left here that they’ve had very steady kidney function for a long time. Now at this point, they were becoming unwell. They not been well for about a year. And around about here, he was started on a proton pump inhibitor. This is shown in larger scale on the right hand side, and then his kidney function plummeted. But even on this scale, this is over six or seven months. So this had been going on for a long time before he got blood tests that showed that he had an eGFR below 10. Kidney biopsy showed a raging acute interstitial nephritis with no particular diagnostic features.

Although the books (often also exam questions) say that you it is common to have a peripheral eosinophilia, skin rash, fever, a whole range of manifestations with AIN, in clinical practice these are uncommon.

This responded to steroids, and it’s a really important point that transplant rejection and tubulo-interstitial nephritis of almost any cause is steroid-sensitive. In this case, it wasn’t the perfect response, probably because it had been going on so long. So he’s still left with chronic renal impairment, eGFR round about 40.

Here’s an example that responded better to steroids, but later relapsed. In this case the diagnosis is sarcoidosis. So it’s one of the autoimmune causes, probably – if we understand the cause of sarcoidosis. This woman in her fifties presented with really quite poor kidney function and a classic chest X-ray of sarcoidosis, showing hilar lymphadenopathy. It responded well to steroids, which because it was sarcoidosis and she had some lung disease as well, she was continued on steroids for quite a long period. Then taken off them and had a relapse, treated for a short time. And then another, severe relapse. But again, recovered pretty good renal function, back up to an eGFR around about 60. And has remained on immunosuppression since, till just recently we’ve tried without it. (Cross fingers)

Infectious causes

Normal again on the left, and on the right, it’s barely possible to recognize the tubular outlines. The cells that you can see in the dilated tubules, and many of the cells infiltrated into the interstitium, are neutrophils. This is classic of acute pyelonephritis caused by the typical organisms that cause urinary tract infections, but clearly capable of causing severe destruction in severe examples like this. Responds to antibiotics, and it would definitely be a bad idea to give steroids. Other microorganisms can do this as well, including mycobacteria, and an occasional challenge is virus infections.

This 20-year-old man had a kidney transplant a couple of years ago, and has now come in with a fever, haematuria, and a severe drop in his estimated glomerular filtration rate (eGFR) down from 60 down to 15. It wasn’t at all clear what was going on. The tests for routine viral infections, including ones that routinely affect the kidney, were negative. And it was only after he had been treated with pulsed steroids for presumed rejection that the result came back, which showed that he had Adenovirus infection affecting his kidney. Shown by brown staining of tubular cells with antibody to Adenovirus (photo not shown). Anti-SV40 was negative – that’s the reagent for BK virus, which is a common post-transplant problem, and so was anti-cytomegalovirus (CMV), which again is a common post-transplant problem, but doesn’t usually cause such a severe nephritis.

Toxic (Noxious) causes

It starts with mushrooms, this tale. These on the right, which were picked by a medical party out in the woods for a weekend in the north of Scotland. They picked some and made some soup. One of the party didn’t like mushrooms so much, but the other two were quite unwell the next day, and a few days after that, they were dialysis-dependent. And they remained that way, without recovery. Picking food mushrooms is usually the explanation for this. But some people are looking for magic mushrooms (left).

These toxic mushrooms, Cortinarious speciossum, grow in Scandinavia and in the north of Scotland. That medical tale was the worst I had to tell for a while until in 2008, almost an identical event happened to Nicholas Evans, author of the Horse-Whisperer, when a guest visiting a Scottish country estate. This time three out of four developed severe renal impairment from a single meal.

A more common plant nephrotoxin comes from Aristolochia clematis. This has on several occasions been picked in mistake for a therapeutic herb. An epidemic was spotted in Belgium in 1993, where some ‘slimming’ herbs, a so-called Chinese herb preparation, contained Aristolochia in place of Stefania.

The patients got an acute interstitial nephritis, as you see in these earlier pictures shown at the top. But if they carried on repeated exposure to the toxin, they cause this remarkable phenomenon. Here sitting in a sea of fibrous tissue, with no recognisable tubules at all, some glomeruli rather extraordinarily seem to have remained alive, without a nephron. And here also is exactly the same appearance from two patients exposed in the same way in London in 1999.

Now, this may sound like an occasional mishap, but it turns out that this same herb is responsible for a longstanding disease which we used to call Balkan Nephropathy. Here, in a patchy geographical distribution, Aristolochia clematis contaminates cereal crops as a weed. In certain villages, there was a very high incidence of unexplained chronic renal failure. There may well be other parts of the world where this happens, either as a herbal treatment, or  through accidental contamination of grain.

Now, briefly, an auto-toxin. Again, what we see here is a very severe interstitial nephritis with one different feature. These very homogenous, funny-looking casts , sitting in some dilated tubules. There’s a couple of other funny things about them. The larger one seems to have fractured in two places. But a more common and typical feature is the cellular reaction around the cast on the right. There’s more elsewhere on cast nephropathy caused by myeloma light chains.

Now with those toxins and myeloma, we’re definitely moving into the territory of chronic interstitial nephritis. Which just indicates that anything that causes acute interstitial nephritis and persists can cause chronic interstitial nephritis. But there are also some unique things that come into the chronic list as well. There’s more about this on the parent page of this one, Interstitial Renal Disease. Thanks for listening.

Further info

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• Read more like this at MedCAL Renal