Drugs and toxins are well established causes of renal
tubulointerstitial injury, however drug-indued glomerular diseases are
also an important concern for clinicians.
The glomerular insult associated with drug exposure can be broadly
classified into two specific forms: (1) direct cellular toxicity and (2)
immune mediated injury.
Direct glomerular cell injury, involving the mesangial, endothelial and
visceral epithelial cells.
Visceral epithelial cell, drug induced podocytopathy can occur in a
number of situations.
IFN therapy is associated with podocyte injury that can manifest as
nephrotic syndrome and histologic lesions, including MCD or FSGS,
of both the collapsing and noncollapsing variety.
Pamidronate in high doses cause direct podocyte injury with impaired
cell energetics, disrupted cytoskeleton, or altered cell signaling.
Chronic lithium exposure can be associated with MCD and less
NSAIDs may be a cause of MCD which may be because of shunting of
AA metabolites into pathways that alter immune function and
promote podocye injury.
Both sirolimus, and androgenic anabolic steroids frequently abused by
bodybuilder can cause FSGS lesion seen on biopsy.
Endothelial cell: TMA is a severe form of endothelial injury that
occurs systemically and within the renal parenchyma. A drug induced
etiology should always be considered including chemotherapeutic
agents, IFN, antiplatelet agents, calcineurin inhibitors and quinine.
Mesangial cell injury: Nodular glomerulosclerosis has emerged as a
specific lesion associated with cigarettes smoking.
Immune mediated injury: Exposure to certain drugs can elicit an
immune response that result in generation of autoantibodies and
clinical autoimmune disease, including immune complex or pauci
ANCA associated vasculitis: Drugs commonly implicated in AAV
involve cocaine, levamisole, hydralazine, antithyroid medications,
minocycline, allopurinol, penicillamine, and sulfasalazine.
Drug induced lupus: The drugs commonly associated with DIL are
hydralazine, procainamide, and anti-TNF therapy.
Membranous nephropathy, which can be induced by gold salts,
captopril (the only ACE-I), and NSAIDs.
Finally we conclude that, a variety of drugs have the capacity to induce
glomerular injury. These drug induced glomerular disease should be
part of the differential diagnosis in patients presenting with
proteinuria, hematuria, and/or renal insufficiency. Recognition of a
drug induced etiology and withdrawal the offending drug providing
the best hope of renal recovery.