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chronic interstitial nephritis (analgesic nephropathy, drug-induced chronic interstitial nephritis)
Etiology:
1) medications
a) chronic analgesic use (daily use for years)
- patients generally do not admit to analgesic abuse
- aspirin or acetaminophen* alone does not cause analgesic nephropathy, but many NSAIDs may [1]
- celecoxib
b) sodium phosphate
c) orlistat, high doses of vitamin C
d) lithium
e) calcineurin inhibitors (cyclosporine, tacrolimus)
f) proton pump inhibitors
g) H2 blockers (ranitidine, famotidine, nizatidine, cimetidine)
h) allopurinol
i) antiretrovirals (indinavir, abacavir, tenofovir)
j) diuretics (triamterine, furosemide, thiazides)
k) anticonvulsants (phenytoin, carbamazepine, phenobarbital, valproate)
l) mesalamine
m) antibiotics (cephalosporins, fluoroquinolones. penicillins, rifampin. sulfonamides)
i) chemotherapeutic agents
- cisplatin, carboplatin, cyclophosphamide, ifosfamide, methyl CCNU, BCNU)
k) immunosuppressive agents
- cyclosporine, tacrolimus
2) toxins
- Balkan endemic nephropathy
- heavy metal poisoning
3) autoimmune
- anti-tubular basement membrane Ab
- sarcoidosis
- Sjogren's syndrome
- systemic lupus erythematosus
- IgG4-related disease
- tubulointerstitial nephritis with uveitis
4) hereditary
- medullary cystic kidney disease
- mitochondrial disorders
- nephronophthisis
5) infections
- polyoma BJ virus (post renal transplantation)
- brucellosis
- cytomegalovirus
- Epstein-Barr virus
- Hantavirus
- HIV1 infection
- hepatitis B
- mycoses
- Legionellosis
- tuberculosis
- toxoplasmosis
- chronic pyelonephritis
6) malignancies
- leukemia
- lymphoma
- multiple myeloma
7) hypertensive nephrosclerosis
8) obstructive uropathy
- nephrolithiasis
- vesiculoureteral reflux
9) hyperuricemia
* ref 2 indicates acetaminophen alone may cause analgesic nephropathy
Epidemiology:
1) 20% of cases of tubulonephritis
2) 85% of patients are women
Pathology:
1) phenacetin & its metabolites are concentrated in the renal papillae
2) these metabolites damage the papillae by lipid peroxidation
3) aspirin diminishes local renal blood flow
4) a total dose of 1 kg of phenacetin or 1 g/day for 3 years is necessary to cause analgesic nephropathy
5) transitional cell carcinomas are more common in patients with analgesic nephropathy
6) patients have accelerated atherosclerosis
7) papillary necrosis (30%)
8) interstitial scarring, fibrosis, renal tubular atrophy
9) renal concentrating deficits
Clinical manifestations:
1) chronic pain problem, but may present as flank pain
2) arthritis & muscular aches
3) headache (80%)
4) history of peptic ulcer (40%)
5) hypertension (40%)
6) urinary tract infections with dysuria (25%)
7) history of urinary obstruction (10%)
8) polyuria, nocturia due to renal concentrating deficits
9) hematuria
10) predisposition to volume depletion
11) NSAID-induced interstitial nephritis may present as nephrotic syndrome
12) premature aging
13) slow decline in renal function over months-to-years
14) Fanconi syndrome
15) normal anion gap metabolic acidosis (RTA1 or RTA4)
Laboratory:
1) anemia (85%)
2) urinalysis
a) sterile pyuria
b) hematuria
c) isosthenuria (urine concentrating deficit)
d) urine protein may reveal nephrotic syndrome, but generally < 1500 mg/24 hr
3) serum albumin may be low with nephrotic syndrome
4) basic metabolic panel
- decline in GFR
4) autoantibodies to TINAG
Radiology:
1) renal ultrasound: small kidneys (50%)
2) normal excretory urogram (10%)
3) papillary calcification & papillary necrosis may be seen with:
a) intravenous pyelogram (IVP)
b) computed tomography (CT)
Complications:
- may progress to end-stage renal disease
Management:
1) discontinue offending agent
2) supportive measures
Related
acute interstitial nephritis
renal papillary necrosis
General
interstitial nephritis
chronic kidney disease (CKD)
References
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 612
- Medical Knowledge Self Assessment Program (MKSAP) 11, 18, 19.
American College of Physicians, Philadelphia 1998, 2018, 2021.
- eMedicine: Nephritis, Interstitial
http://www.emedicine.com/med/topic1596.htm
- Analgesic Nephropathy (Painkillers and the Kidneys)
http://kidney.niddk.nih.gov/kudiseases/pubs/analgesicnephropathy/index.htm