Drug-induced glomerular disease: direct cellular injury

Abstract

The potential of medications to cause kidney injury is well known. Although nephrotoxicity is most commonly associated with injury in the tubulointerstitial compartment as either acute tubular necrosis or acute interstitial nephritis, a growing body of literature has also highlighted the potential for drug-induced glomerular lesions. This review surveys the three primary patterns of drug-induced glomerular diseases stratified by the cell type at which the glomerular lesion is focused: visceral epithelial cell (or podoctye) injury, endothelial cell injury, and mesangial cell injury. A number of commonly prescribed medications, including IFNs, bisphosphonates, nonsteroidal anti-inflammatory drugs, antiplatelet agents, and antiangiogenesis drugs, that are both prescribed and available over the counter, have been implicated in these iatrogenic forms of glomerular disease. Recognition of these drug-induced etiologies of glomerular disease and rapid discontinuation of the offending agent are critical to maximizing the likelihood of renal function recovery.

Keywords: GN; drug nephrotoxicity; glomerular disease.

Figure 1.

Drug-induced epithelial cell injury. (A) A glomerulus from a patient treated with pamidronate exhibits collapsing FSGS with global wrinkling and retraction of the glomerular basement membrane associated with swelling and proliferation of overlying epithelial cells. Jones methenamine silver, ×600. (B) In this patient treated for multiple sclerosis with IFN-β, glomeruli appear unremarkable by light microscopy. On ultrastructural evaluation, complete foot process effacement, diagnostic of minimal change disease, is seen (×6,000).

Figure 2.

Drug induced TMA. (A) A glomerulus from a patient treated with gemcitabine exhibits subacute findings of thrombotic microangiopathy, including global double contours of the glomerular basement membrane (tram tracking), cellular interposition, and dissolution of the mesangial matrix consistent with mesangiolysis. Mild swelling of endothelial and visceral epithelial cells is also noted. Jones methenamine silver, ×600. (B) A glomerulus from the same patient exhibits a fresh fibrin thrombus in a preglomerular arteriole. Hematoxylin and eosin, ×600. TMA, thrombotic microangiopathy.

Figure 3.

Nodular glomerulosclerosis of smoking. Pathologic findings in smoking-associated nodular glomerulus resemble changes seen in nodular diabetic glomerulosclerosis and include nodular mesangial sclerosis with thickening of glomerular and tubular basement membranes. Periodic acid–Schiff, ×500.