4.2.2 Acute interstitial nephritis (AIN) with granulomas

Definition: AIN with poorly defined granulomas consisting of epitheloid cells, histiocytes and lymphocytes in the tubulo-interstitial space

Granulomatous interstitial nephritis (a granuloma turns an acute interstitial nephritis into a granulomatous interstitial nephritis) can be associated with both eosinophilic leukocytes and plasma cells. Tubules lying in the centre of granulomas are destroyed. The granulomas are often not clearly defined and, rarely, contain only a few giant cells. These are found next to or in the vicinity of one or more tubules. They are composed of lymphocytes and histiocytes/epithoid cells. Granulomas must be systematically searched for in acute interstitial nephritis, since their presence is the only pointer to a poor prognosis due to destruction of the parenchyma by  granulomas. Granulomas can occur with any known noxia that can cause acute interstitial nephritis.

With AIN of prolonged course (longer than a month) edema can be replaced or accompanied by discrete interstitial fibrosis. This may, depending on the extent of AIN, affect the tubulo-interstitial space in a sometimes focal, sometimes diffuse manner. The tubuli are however in these areas of fibrosis usually only forced apart and only later tubular atrophy develops.

Patients with documented AIN can, following  repeated intake of the same substance, develop a granulomatous AIN, that in the worst case can lead to irreversible, terminal renal insufficiency.

Differential diagnosis and comment

In cases of typical tuberculous granulomas, or granulomas typical for sarcoidiosis or fungi, one should not refer to granulomatous interstitial nephritis, but rather use the name of the specific disease in question. 

Tricky  are granulomatous reactions in areas surrounding  trapped Tamm-Horsfall protein casts. In the tubular lumens they are often surrounded by proliferated epithelial cells, but not giant cells, as in cast nephropathy. Moreover, Tamm Horsfall protein casts display a fibrillar substructure in the PAS-stain, whereas the paraprotein casts in cast nephropathy are glassy.  Tamm-Horsfall protein casts may cause necrosis of adjacent epithelial cells so that the Tamm-Horsfall protein may pass through the basement membrane and come to lie in the interstitium. Here they are often surrounded by histiocytes and few lymphocytes, individual eosinophils may be present as well but no giant cells are found. Minimal fibrosis may develop in the surrounding. These may occur in AIN, but should not be referred to as granulomatous AIN. They are often found in other renal diseases with disturbed urinary flow without having prognostic significance.