Interstitial renal diseases

Interstititial kidney diseases (affecting tubules and interstitium) and how to spot them. 30 mins.

Neil Turner, Professor of Nephrology. Part of  Renal Medicine in the Edinburgh MBChB.

The two most important pathologies are

• Acute tubular necrosis (ATN), dealt with under AKI (acute kidney injury).
• Acute Interstitial Nephritis (AIN), dealt with here.

Interstitial diseases also include

• Chronic tubulointerstitial nephritis – of course overlaps with AIN, but extends beyond it, with some interesting new culprits – some listed below.
• Inherited diseases including PKD and other cystic diseases, and some other less common, but fascinating conditions. These are covered in genetic and congenital kidney diseases (MedCal, about half of its 30 mins if your follow up cystic diseases).

How interstitial diseases present

Glomerular diseases are often spotted through causing haematuria and proteinuria, and high blood pressure (though they don’t all do all of those things).Interstitial diseases are much less likely to cause these, especially if acute, and they are often picked up on blood tests in someone who is non-specifically unwell. Which is frustrating, as early diagnosis can make an important difference to outcome.

Acute Interstitial Nephritis

Three main categories of causation – note the mnemonic AIN. While most glomerular diseases are (auto)immune, most interstitial diseases are

• Allergic: an allergic reaction to a drug is most common, but occasionally autoimmune. Acute rejection of a kidney transplant looks the same.
• Infections: Pyelonephritis is acute bacterial infection. Some viruses cause acute interstitial nephritis, and unusual bacteria can, as in leptospirosis.
• Noxious: toxins: plant toxins, chemical toxins. Although in the developed world, more commonly certain immunoglobulin light chains form autotoxins – myeloma kidney (cast nephropathy).

This 13 min video illustrates and expands a little on each:

Chronic interstitial nephritis

A mixed bag and definitely getting too small print for undergraduates here, but it’s an interesting list, that includes

• Any cause of AIN that persists, including allergic with continuing exposure to cause.
• Residual damage from AKI.
• Reflux nephropathy and renal dysgenesis looks mostly fibrotic and chronic inflammatory, if you biopsy it.
• Some inherited disorders.

The three classes of disorder most commonly causing AIN have some different members

• (Auto)Immune – notable causes are Sarcoidosis (granulomatous, often with high Ca++); Sjogren’s Syndrome; and TINU, which stands for TubloInterstitial Nephritis with Uveitis.
• Infective – especially TB, but BK virus is a particular problem after renal transplantation.
• Noxious – exogenous or endogenous toxins
  • Heavy metals (notably lead),
  • Plant toxins – aristolochic acid (Balkan nephropathy, ‘Chinese herb’), toxin from Cortinarius mushrooms, and probably others unknown.
  • Immunoglobulin light chains (myeloma).
  • DRUGS acting other than through allergy: include Lithium, Calcineurin inhibitors (Tacrolimus, Ciclosporin), Tenofovir.

And some interesting additions

• Things causing nephrocalcinosis – includes hyperoxaluria of genetic, gastrointestinal, or dietary origin.
• CKDu (u=unknown) locally endemic at high frequency in some tropical agricultural communities – probably toxic.
• Papillary necrosis/ ischaemic (analgesic nephropathy, bends ‘Caisson disease’, sickle, diabetes)

Now some cases

• A 44 year old man with previous interstitial nephritis (EdCases, concerns long term effects, quite difficult).
• A query from the bone marrow transplant unit (EdCases, complex, interstitial nephritis is among possibilities)
• More to follow

Further info

• Myeloma and the kidney (MedCal; 20 mins)
• Genetic causes (MedCal; 5 mins of this is tubulointersitial).
• Historical glimpse of lead nephropathy. It was endemic in the lead-mining regions and in some industries. The painters of the first Forth (Railway) Bridge got it, but it hasn’t gone away worldwide.

First published May 2020. Rewrite Sep 2020. Credits: histology from Dr Chris Bellamy and Dr Rashmi Lahiri.