Tubulointerstitial nephritis
Lívia Jánoskuti
Definition
• Kidney diseases that involve structures in the
kidney outside the glomerulus
• Tubules and/ or the interstitium
• Tubules are responsible for concentrating the
urine(osmolality, sodium and water reabsorption)
• Reduction of tubular or interstitial function both
result in: impaired resorptive capacity
• Isosthenuria:urin osm. the same as blood
< 350 mosmol/kg
Characteristics of tubulointerstitial
and glomerural diseases
Tubular
Glomerular
Urine osmolality
Low <350mos/kg
High/norm
Urine sodium
>40mM/L
<40
U. sediment
hematuria
Muddy brown
Red cell casts
casts(ATN)
Eosinophils(AAIN)
rare
common
proteinuria
rare
common
Causes
Concom.illness
Drugs common
Autoimmun or
congen.
Therapy
Supportive/dialysis Steroids,immunmo
Eosinophils and eo.in casts in urine sediment
(Hansel’s stain)
Muddy brown casts
pigmented granular casts
Pathophysiology
• Lethal, sublethal injuri to renal cells lead to
expression of new local antigens, inflammatory
cell infiltration and activation of proinflammatory
cells and cytokines
• Acute- renal tubular dysfunction with or without
renal failure ( If the tubular basement mebrane is
preserved- reversibile)
• Chronic- interstitial scarring fibrosis, tubule
atrophy- resulting progressive renal failure
Clinical presentation
Acute
• Abruptly, within days of exposure to the
offending agent
• Uremic symptoms: oliguria
Acute tubulointerstitial diseases
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Acute tubular necrosis(ATN)
Contrast nephropathy
Acute allergic tubulointerstitial nephritis(AAIN)
Atheroembolic renal insuff.
Pigment mediated renal insuff.
Crystal mediated renal insuff.
Myeloma related renal insuff.
Toxin mediated renal insuff.
Papillary necrosis.
Acute tubular necrosis
• Cause:hypotension or sepsis
• Sy: azotemia as incidental findings
• Dg: U osm-L,UNa –H,FENa-H BUN/cr –L
muddy brown casts
• Th:supportive
observation electrolytes, mental status,
fluid overload, -dialysis
Lab. Findings distinguishing ATN
from prerenal azotemia
prenrenal
ATN
U Na mM/L
<20
>40
FE Na
<1%
>1%
U osm mM/kg
>500
<350
BUN/creat
>20:1
10-15:1
U sediment
Hyalin casts
Brown casts
Contrast nephropathy
• Progressive rise in Se creat 24-48 h after
radiocontrast is given
• Risk factors: older age, DM, HF,MM. preexisting
chr.kidney disease,liver failure
• Th:supportive
• Prevention:avoiding contrast(when possible),
low dose low osmolality contrast agent use,
isotonic fluid infusion 1ml/kg/h 6-12h before and
after the contrast,600mgacetylcystein pos before
the day and the day of contrast
Acute Allergic Interstitial
Nephritis(AAIN)
Causes(many):
drugs(allopurinol,penicillin, quinolons,
sulfas, rifampicin)
infection,autoimmune disease
Sy:shortly after the first dose;fever,rash
Dg:eosinophilia, eosinophils in u.sediment.IgE elev
Th:stop offending agent, renal f. control,
• no sign of improvement within few days- 1mg/kg
prednisolon for 4-6 weeks with rapid tapering of
the dose
Atheroembolic kidney disease
• Cause:multiple small infarctions of renal
parenchyma secondary to recent vascular
procedure ( angio, PTCA)
• (cholesterol crystals lodge in small/medium
sized arteries)
• Sy: bluish skin discolor., livedo reticularis
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uremic sy.Hollenhorst plaques in optic fundi
• Dg.retrospective
• Th: no therapy
Livedo reticularis
Blue toe syndrome
Hollenhorst plaques
( bright plaques in the retinal arterioles
Pigment mediated RI.
Cause:
-rhabdomyolysis(traumatic crush injury, muscle
ischaemia,seizures, statins,NSAID, cocaine
overdose),
-intravasc. hemolysis ( blood transfusion
reaction)
Sy: very dark urin, uremic sy.
Dg: Hbg, myoglobin in urine, CPK,Se K
Th:ICU- hyperK-Ca gluconate iv, osmotic
diuresis(mannitol), alkalization( sodium
bicarb)can reduce liklehood of renal insuff.
Gross hemoglobinemia and
hemoglobinuria
Crystal mediated RI.
Cause:
1.Oxalate crystals (ethylen glycol
toxicity,methoxyflurane anaesthesia, Crohn s
disease)
2.urate crystals –tumor lysis syndr., primary, sec.
hyperuricaemia if the urine concentrated
Dg:history
1.envelope shaped crystals , anion gap
metabol.acidosis(Na)-(Cl+HCO3)>11mEq/L
2.Hyperuricaemia, diamond shaped crystals
Th: 1.aggressive hydration+10% ethanol 7,5mg/kg
iv for ADH enzime competition
2.aggressive hydration + allopurinol
Myeloma-related RI.
Cause:overproduction of monoclonal Ig light
chain( Bence Jones protein) by pathologic
B cell clonal population
Sy: MM and uremic
Dg. 24h urin protein ELFO
Th: MM therapy.
Toxin mediated RI
Cause : drugs, but not occure after the first
dose (NSAID,aminoglycoside,
amphotericinB, cisplatin, cephalopsorins,
cyclosporin)
Sy: uremic, following longer term th.(daysweeks) No fever, no rash
Th:dependent on drug.
Prevention: ensure widest spacing of dose,
estimation of drug plasma levels
Papillary necrosis
Cause: NSAID, acetaminophen ingestion in
patients with DM, liver cirrhosis, sickle cell
disease
Sy: fever,flank pain( appears like UTI)
Dg: no WBC or elevated nitrits in urin.
Elevated serum WBC
Confirm with spiral CT.
Th: stop offending drug.
Prevention: avoid excessive use of NSAID
Principal mechanism in acute
tubulointerstitial nephritis
• Hypersensitive reaction to drugs
(penicillin, NSAID, sulfa drugs)
• Infection (viral, bacterial, parasitic) often
associated with obstruction or reflux
• Autoimmun mechanism
• Vasomotor nephropathy (afferent arteriola
constriction)
• Intratubular obstruction (pigment, crystal,
protein)
• Direct toxic effect on tubular epithelium
Clinical presentation
2.Chronic
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Drugs (analgetics, lithium, cylosporin, tacrolimus)
Heavy metals ( lead, cadmium, mercury)
Obstructive uropathy, nephrolithiasis, reflux disease
Immunologíc diseases( lupus, Sjögren,sarcoidosis,
vasculitis, chr. transplant rejection
Neoplasia ( myeloma, amyloidosis, leukemia)
Atherosclerotic kidney diseases
Metabolic ( hyperCa,potassium depletion, cystinosis)
Genetics( Alport sy, medullary cystic diseases
Miscellaneous ( Balkan endemic nephropathy)
Epidemiology
• 10-15% of all kidney diseases
• Analgesic nephropathy is 5-6 times more
common in women
• All toxic nephropathies are observed more
frequently with adavancing age
(cummulative effects)
Clinical presentation
Chronic
• Insidious nature
• Often diagnosed incidentally on routine
laboratory screening, or evaluation of
hypertension
• Modest proteinuria, sterile pyuria, anemia, renal
insuff ( NSAID)
• Polyuria concentration defect (lithium)
• Modest proteinuria, hyperK renal tub. acidosis in
chr. obstruction
• Arterioscler. kidney: modest proteinuria,
kreatinin and BUN elevation, hypertension
Laboratory
• BUN , kreatinin- renal failure
• Low bicarbonate < 24 mEq L- acidosisph<7,35
With hypoK – proximal tub. disorder
With hyperK- distal tub disoreder
• Urinalysis: hematuria and pyuria with-or without
bacteria, casts, eosinophils, crystals
• Urine protein usually less >1-2 gr/24h
• Protein ELFO- low mol. weight (beta-2
microglob,alfa-1 microglob., light chains)
Imaging
US/ and flat plate kidney- hydronephrosis, renal
calculi
• Normal kidney size favours acute
• Small kidneys with increased echogenicity- chr .
disease
Iv pyelography usually not indicated- contrast
damage
CT(high resolutional) scan show
microcalcifications in renal papillary tipsdiagnosing analgesic nephropathy
Nephrosclerosis CT
Hydronephrosis US
Analgesic nephropathy CT
microcalcifications
Management of chr.
Tubulointerstitial disease
• Depends on the etiology- generally stop of the
offending drug and supportive measures-blood
pressure and anemia control
• Analgesic- increased uroepitheal cc
• Lead- chelation th. with EDTA
• Atheroscler.- no specific th.-smoking cessation,
cholesterol diet and statins
• Reflux nephropathy, urinary tract
obstruction:surgical treatment, antibiotics
Lead nephroptahy diagnosis
• Bone lead content by radiographic
fluorescensce
• EDTA lead mobilizatiion test: after iv/im 2 g
EDTA( calcium disonium versenate) 24h
urine lead exretion->0,6 g- abnormal
• Basophil puncture in RBC
Prognosis
• Most patients with allergic inerstitial
nephritis recover upon cessation of the
offending agent
• Cholesterol microembolic diseases have
some spontaneous improvement,
complete resolution is rare
• Chr. Tubulointerstitial d. progresses to
ESRD.