Tubulointerstitial nephritis

Lvia Jnoskuti

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

Muddy brown
Red cell casts
casts(ATN)
Eosinophils(AAIN)

hematuria

rare

common

proteinuria

rare

common

Causes

Concom.illness
Drugs common

Autoimmun or
congen.

Therapy

Supportive/dialysis Steroids,immunmo
dulators

Eosinophils and eo.in casts in urine sediment

(Hansels 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

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

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

Drugs (analgetics, lithium, cylosporin, tacrolimus)

Heavy metals ( lead, cadmium, mercury)
Obstructive uropathy, nephrolithiasis, reflux disease
Immunologc diseases( lupus, Sjgren,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.