Chronic Tubulointerstitial Nephritis Flashcards
Background on CTIN
CTIN is characterized by tubulointerstitial scarring and fibrosis, tubular atrophy, with or without significant macrophage and lymphocytic infiltration.
CTIN
Clinical Manifestations of CTIN
Patients are typically asymptomatic with incidental abnormal laboratory findings:
Mild proteinuria < 1.5 to 2.0 g/d
CTIN
Clinical Manifestations of CTIN
Proteinuria is predominantly LMW proteins.
“Bland” urinalysis: no (or rare granular) casts, minimal white and/or red blood cells
CTIN
Clinical Manifestations of CTIN
Anemia severity out of proportion to degree of kidney injury due to damage of peritubular erythropoietin producing cells
CTIN
Clinical Manifestations of CTIN
Other signs of tubular injury may be present: sodium wasting, metabolic acidosis, Fanconi syndrome, nephrogenic insipidus.
CTIN
Histopathology of CTIN
Fibrotic hypocellular interstitium
Tubular Atrophy
CTIN
Causes of CTIN
Common causes (drugs, crystals [e.g., calcium phosphate, uric acid, oxalate], infections, autoimmune, obstruction, chronic ischemia, heavy metals)
CTIN
Causes of CTIN
Drug-induced CTIN:
Analgesic nephropathy:
Traditionally referred to the chronic use of the drug mixture containing (phenacetin, paracetamol, or acetaminophen) plus (salicylate) plus a potentially addicting agent (caffeine or codeine). Any of the drugs belonging to the first group can be metabolized to acetaminophen and subsequent toxic metabolites which require glutathione for detoxification. Accumulation of these toxic metabolites may form covalent bonds with kidney tissue and induce tissue injury and vascular endothelial damage. Salicylate is a glutathione depletor which can limit the neutralization process of toxic metabolites of acetaminophen.
CTIN
Causes of CTIN
Drug-induced CTIN:
Analgesic nephropathy:
Analgesic nephropathy affects predominantly the medulla and papillary tip. Characteristic presentations include CKD, CT revealing papillary necrosis and calcifications, or kidney ultrasound revealing small echogenic kidneys
CTIN
Causes of CTIN
Drug-induced CTIN:
Analgesic nephropathy:
Single analgesic use may also lead to analgesic nephropathy.
Acetaminophen:
There are data to suggest that chronic, daily, high dose use of acetaminophen may lead to long-term nephrotoxicity in women.
CTIN
Causes of CTIN
Drug-induced CTIN:
Analgesic nephropathy:
Salicylates: Most studies suggest that the long-term use of daily therapeutic dose of aspirin (ASA) alone (i.e., without concurrent use of acetaminophen) do not lead to kidney injury.
CTIN
Causes of CTIN
Drug-induced CTIN:
Analgesic nephropathy:
NSAIDS:
High dose of NSAIDS may induce CKD in those with underlying or high risk for kidney injury, but not in healthy individuals.
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury:
Chronic interstitial nephritis: characterized by cortical and medullary distal and collecting tubular dilatations/cysts, tubular atrophy, and interstitial fibrosis
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury:
Toxic intracellular lithium levels are thought to alter primary cilia function and lead to tubular cyst formation.
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury:
Commonly associated glomerular lesions: global sclerosis, FSGS, minimal change disease.
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury:
Lithium may also be associated with nephrogenic diabetes insipidus, distal RTA, hypercalcemia, and hypothyroidism.
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury
Histopathology:
Severe lithium-associated tubulointerstitial nephropathy with diffuse interstitial fibrosis, tubular cysts, dilations, and tubular atrophy (flattened tubular epithelial cells) and relative sparing of glomeruli. Tubular cysts may be evident on CT imaging.
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury
Management:
Discontinue lithium if safe and possible (there are reports of patients committing suicide with lithium discontinuation).
Routine CKD management to slow down progression of disease
CTIN
Causes of CTIN
Drug-induced CTIN:
Lithium-induced kidney injury
Management:
Amiloride may be considered to reduce lithium reabsorption at collecting tubules.
Thiazides may be considered in the treatment of nephrogenic diabetes insipidus.
CTIN
Causes of CTIN
Drug-induced CTIN:
Famotidine:
case report of famotidine-induced autoantibody formation against carbonic anhydrase II in the kidneys
CTIN
Causes of CTIN
Infection-related CTIN:
Malakoplakia:
Rare granulomatous disease of infectious etiology (bacterial, fungal, tuberculosis, etc.)
CTIN
Causes of CTIN
Infection-related CTIN:
Malakoplakia:
Presents as friable yellow plaques that may involve urinary tract, GI tract, other visceral organs, skin (erythematous nodular lesions, ulcerations, to draining fistulas/abscesses).
CTIN
Causes of CTIN
Infection-related CTIN:
Malakoplakia:
Seen in immunocompromised hosts (e.g., diabetes mellitus, malignancy, malnutrition, alcoholism, immunosuppressive therapy)