Interstitial nephritis induced by drugs and toxins

Know the drugs that can cause acute drug-induced (hypersensitivity) interstitial nephritis

• Sulfonamides

• Synthetic penicillins

• Rifampin (other synthetic antibiotics)

• Thiazide diuretics

• Phanylbutazone (NSAIDs)

• Phenindione

• Cimetidine

Know the urinary findings and histology in ADIIN

• Hematuria

• Mild proteinuria

• Leukocyturia (including eosinophils)

• Elevated serum creatinine or ARF w/ oliguria in 50% of cases

• Interstitial edema and infiltration by mononuclear cells

• Eosinophils and neutrophils commonly in large numbers

• Methicillin / thiazides – interstitial granulomas w/ giant cells may be seen

• NSAIDs may cause minimal change disease and nephrotic syndrome

Know the mechanisms of ADIIN

• May be due to IgE-mediated late-phase hypersensitivity

• Drugs likely act as haptens

• During secretion by tubules, drugs covalently bind to cytoplasmic / extracellular component of tubules and become immunogenic

Know the minimal dose required for the development of renal damage in analgesic nephropathy

Know the histology of analgesic nephropathy

• Papillae show various stages of necrosis, calcification, fragmentation, and sloughing

• This is different from papillary necrosis associated w/ DM (in which they are all at the same stage of necrosis)

• Loss and atrophy of cortical tubules

• Interstitial fibrosis and inflammation

• Cortical columns of Bertin are spared

• Small vessels exhibit characteristic PAS+ BM thickening (analgesic microangiopathy)

Know the mechanism of renal damage, clinical manifestations and complications of analgesic nephropathy

• Early findings include inability to concentrate urine (due to papillary damage)

• Acquired distal renal tubular acidosis contributes to development of renal stones

• Headache, anemia, GI symptoms, and HTN are common accompaniments

• Complication with UTI in 50% of cases

• Gross hematuria or renal colic if large amounts of necrotic papillae are excreted

• Progressive impairment leads to chronic renal failure, while removal of drug tends to stabilize or improve renal function

• Transitional papillary carcinoma of the renal pelvis is a very rare complication found in those who discontinue the drug

Know the mechanism of renal damage and different morphologic features in NSAID-induced nephropathy

• Hemodynamically induced acute renal failure due to inhibition of prostaglandin synthesis

• Acute hypersensitivity interstitial nephritis (see above)

• Acute interstitial nephritis and lipoid nephrosis, producing renal failure and nephrotic syndrome

• Membranous glomerulonephritis, leading to nephrotic syndrome

Category: Pathology Notes