Week 4: tubulointerstitial nephritis and drug nephrotoxicity Flashcards Preview

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Flashcards in Week 4: tubulointerstitial nephritis and drug nephrotoxicity Deck (16):
1

What are the main causes of Acute interstitial nephritis (AIN).

1. Drugs: penicillins, cephalosporins, NSAIDs, sulfonamides, rifampin, indinavir, allopurrinol, PPIs
2. Infections: streptococci, typhoid fever, legionella, leptospirosis, cytomegalovirus
3. Immunological diseases: SLE, Sjogren's syndrome, sarcoidosis
4. Idiopathic with uveitis

2

Define Acute tubulointerstitial nephritis.

-acute renal failure form immune-mediated tubulointerstitial injury, initiated by medications, infection, and other causes
AS OPPOSED TO
ATN: which is acute tubular cell injury/dysfxn. Commonly caused by ischemia and toxic drugs

3

Pathogenesis of AIN

-may be cell mediated or humoral hypersensitivity reactions
-drug/metabolite may act as hapten to form hapten-protein complex that initiate hypersensitive reaction
-others have circulating autoantibodies to tubular antigens and deposition of these antibodies in tubular BM, e.g. SLE patients

4

Clinical features of classic AIN

-asymptomatic with abnormal urinalysis (nephrotic range proteinuria), e.g. NSAIDS
-symptomatic with (hypersensitivity reaction): maculopapular rash, fever, eosinophilia (triad of rash, fever, eosinophila), oliguria possible
-symptomatic e.g. beta lactam antibiotics

5

What are lab findings in AIN?

-Lab studies: elevated Cr, peripheral Eosinophilia
-urinalysis: rbcs, wbcs, leukocyte casts, low grade proteinuria
-urine microscopy: urine eosinophils
-FeNa>1% usually

6

Pathological findings in Drug-induced AIN

-interstitial edema and infilatrate consisting of primarily T lymphocytes and monoctytes
-eosinophils and histiocytes with granuloma formation in 30%, especially after antibiotics

7

Treatment and prognosis of drug induced AIN

-most forms are self limited and resolve upon stopping the drug
-Advanced prognostic features: prolonged renal failure >3 weeks, NSAIDs, certain findings: granulomas, tubular atrophy, fibrosis

8

Mechanisms of NSAID induced AIN

-hemodynamic: blockage of PGl2 and PGE2 (vasodilatory effects) prevent balance of AngII
-allergic
-Na retention by inhibition of COX-2 natriuretic effect
-hyperkalemia (suppressing renin)

9

Pathogenesis of aminoglycoside induced ATN

-filtered and almost entirely excreted in urine
-small amount is taken up and stored by epithelial cells in PT, where they induce acute tubular necrosis

10

Clinical features of aminoglycoside induced ATN

-develops 7-10 days after treatment
-often non-oliguric, urine output>500ml/day
-occasionally occurs several days after drug is discontinued b/c of prolonged storage in PT cells
-supportive treatment, hemodialysis occasionally needed
-risk factors for nephrotoxicity: old age, obesity, preexisting renal insufficiency or liver disease, frequency/duration of drug therapy, concurrent use of other nephrotoxins

11

pathogenesis of radio contrast media-induced ARF

-direct tubular injury, leading to generation of oxygen radicals
-fall in renal perfusion due to contrast induced release of endothelin-->leading to widespread renal vasoconstriction
-histological lesion consistent with ATN

12

Risk factors for contrast nephropathy.

Age (>65)
Cr >1.5
Diabetes
CHF, nephrotic syndrome, liver cirrhosis
Volume depletion
High total contrast dose or repeated exposure over short period of time
Multiple myeloma

13

Clinical course of contrast nephropathy.

-dx made from hx of AFR 24-48 hrs after IV contrast administration.
-nonoliguric ARF
FE[Na]<1%
-UA: renal tubular epithlial casts or muddy brown casts or both
-recovery generally in 1 week
-supportive treatment
-isotonic fluid is only proven prevention

14

Clinical manifestations of amphotericin B nephrotoxicity.

1. Acute renal failure: dose dependent decline in GFR with oliguria or anuria
--tubular membranes toxicity associated with vasoconstriction from drug-->ATN
2. other tubular dysfunction: precedes ARF--hypokalemia, hypomagnesemia, distal tubular acidosis

15

Describe toxicity from gadolinium containing contrast agents

-used for MRIs
-increased toxicity in patients with prolonged hemodialysis
-nephrogenic systemic fibrosis (NSF): large areas of hardened skin with fibrotic nodes dn plaques. flexion contractors,

16

Describe Analgesic nephropathy and clinical features.

-chronic interstitial disease, associated with long term use of analgesics
-believed to be due to 2 analgesics +codeine/caffeine
-classically seen with phenacetin
-most are females in 40s or 50s who complain of chronic pain
-can lead to development of both CTIN and papillary necrosis.
-renal damage primarily in medulla: NSAIDs and ASA inhibit PG production-->vasoconstriction-->ischemia and papillary necrosis
-increased risk of transitional cell CA