Definition

 • Immune injury to the tubules and interstitium leading to AKI.

 Aetiology

 • The main causes are drugs, autoimmune diseases (e.g. SLE, Sjogren’s), and infections.

 • Drug- related tubulointerstitial nephritis (TIN) causes tubular injury through immune hypersensitivity to the drug, rather than through direct nephrotoxic effect of the drug. • Any drugs can cause acute TIN, but the most common culprits are:

 - NSAIDs;

- antibiotics;

 - diuretics;

 - allopurinol;

- proton pump inhibitors.

 Pathogenesis

• A hypersensitivity- type immune reaction to a drug or to an infection, or an autoimmune reaction to local antigens causes a predominantly monocytic tubulointerstitial inflammatory infiltrate. Inflammatory cells cause injury to the tubules and interfere with their normal function.

 Presentation

• The typical presentation is AKI.

 • In drug- related TIN, presentation often occurs within days of starting the drug, though occasionally it only occurs after several months of exposure. Patients often have fever, rash, eosinophilia, eosinophiluria, and raised serum IgE levels.

• Patients with NSAID- induced disease may also show heavy proteinuria related to the concomitant development of MCD.

Histopathology

• The interstitium is expanded by oedema and a predominantly monocytic inflammatory cell infiltrate.

• Lymphocytes are seen infiltrating into the tubules (‘tubulitis’) (Fig. 1).

 • In drug- related TIN, there are often eosinophils.

 • Granulomatous TIN is a subtype of TIN in which histiocytic granulomas are present in the interstitium, sometimes with giant cells, with or without central necrosis. The most common causes are drug- related TIN, sarcoidosis, and mycobacterial infections.

Fig1. Active tubulointerstitial nephritis. Periodic acid– Schiff stain. Lymphocytes and cells of monocytic lineage appear as small dark nuclei amongst the tubular epithelial cells, which have larger nuclei with more dispersed chromatin. Tubulitis is defined by inflammatory cells within the spaces delimited by the tubular basement membranes, seen on this PAS stain as bright pink lines around individual tubular profiles (see Plate 18).

Prognosis

 • Successful treatment of the underlying autoimmune disease or infection, or cessation of the offending drug, may result in complete recovery. A short course of steroids is given to clear the local inflammatory infiltrate and therefore halt further injury to the tubules.