This document discusses various types of acute tubulointerstitial nephritis including those caused by antibiotics, analgesics, heavy metals, and autoimmune diseases. It notes that analgesic nephropathy is more common in women likely due to taking more pain medications. The kidney is resistant to structural damage from bacterial infections without obstruction. Acute tubulointerstitial nephritis can result from hypersensitivity reactions, transplant rejection, or infections from bacteria, viruses, fungi, or parasites. Transforming growth factor beta and nuclear factor kappa B play roles in fibrogenesis and inflammation in this condition.

1. äéÜìåóç óùëçíáñéÜêç íåöñßôéäá ÁÍÔÉÓÔÑÏÖÙÓ, Ç ÑÏÍÉÏÓ ÄÉÁÌÅÓÇ Analgesic nephropathy is 5-6
ÍÅÖÑÉÔÉÄÁ ÁÑÁÊÔÇÑÉÆÅÔÁÉ times more common in
Á Ï: women. This is generally
áèçóåéò ÅÍÄÏÍÅÖÑÉÊÅÓ ÏÕ ÄÅÍ attributed to women taking
ÁÖÏÑÏÕÍ ÔÏ Ó ÅÉÑÁÌÁ = o ÏÕËÏ ÏÉÇÓÇ more analgesics than men.
ÄÉÁÌÅÓÏ ÓÙËÇÍÁÑÉÁÊÅÓ o ÉÍÙÓÇ However, a greater sensitivity to
o ÓÙËÇÍÁÑÉÁÊÇ ÁÔÑÏÖÉÁ the toxic effects of analgesics
or differences in analgesic
ÓÁÖÙÓ ÓÕ ÍÁ ÓÕÍÕ ÁÑ ÅÉ ÁÑ ÏÌÅÍÇ metabolism in women cannot
Ó ÅÉÑÁÌÁÔÉÊÇ ÂËÁÂÇ ÓÅ ÅÄÁÖÏÓ ÌÅ ÑÏÏÄÅÕÔÉÊÇ ÅÎÅËÉÎÇ ÓÅ ÍÁ
be ruled out.
ÅÃÊÁÔÅÓÔÇÌÅÍÇÓ ÄÉÁÌÅÓÏÓÙËÇÍÁÑÉÁÊÇÓ
ÍÏÓÏÕ Ï ÏÕ ÊÕÑÉÁÑ ÏÕÍ ÏÉ ÅÊÄÇËÙÓÅÉÓ Acute tubulointerstitial nephritis
ÔÇÓ Ó ÅÉÑÁÌÁÔÉÊÇÓ ÍÏÓÏÕ ÌÇ ÁÍÉÓÌÏÉ ÏÎÅÉÁÓ ÄÉÁÌÅÓÇÓ
ÍÅÖÑÉÔÉÄÁÓ : (general features)
1..ÁÍÔÉÄÑÁÓÇ Õ ÅÑÅÕÁÉÓÈÇÓÉÁÓ ÓÅ ÔÕ ÉÊÇ ÅÍÁÑÎÇ = ÔÁ ÅÉÁ
Ç ËÅÏÍ ÔÕ ÉÊÇ ÅÉÊÏÍÁ ÅÎÏÑÌÁÔÁÉ Á Ï ÅÃÊÁÔÁÓÔÁÓÇ ÏÍÁ ÊÁÔÁ
ÁÍÏÓÏËÉÃÉÊÇ ÖËÅÃÌÏÍÇ ÖÁÑÌÁÊÁ
ÊÁÍÏÍÁ ÅÍÔÏÓ ÇÌÅÑÙÍ Á Ï
ÅÍÉÊÉËËÉÍÇ – ÖÓÁÖ – sulfa drugs ÔÇÍ ÅÍÁÑÎÇ ÅÊÈÅÓÇÓ ÓÔÏ
ÔÏÎÉÊÏ ÁÑÁÃÏÍÔÁ
2..ÏÎÅÉÁ ÓÙËÇÍÁÑÉÁÊÇ ÍÅÊÑÙÓÇ ÌÓÁÖ : ÌÅÔÁ Á Ï ÅÊÈÅÓÇ
Á ÏÖÑÁÎÇ ‘Ç ÁËÉÍÄÑÏÌÇÓÇ + ÌÇÍÙÍ
ËÏÉÌÙÎÇ o ÅÎÁÍÈÇÌÁ
Acute tubulointerstitial nephritis: o ÕÑÅÔÏÓ
The kidney is remarkably resistant to o ÅÙÓÉÍÏÖÉËÉÁ
o Hypersensitivity reactions (eg, drugs, structural damage in bacterial o ÅÙÓÉÍÏÖÉËÏÕÑÉÁ
penicillins, sulfa drugs, infections, and, in the absence of o ÁÕÎÇÓÇ ÔÙÍ IgE
nonsteroidal anti-inflammatory drugs [NSAIDs] obstruction, damage from bacterial
most common) infection in the kidney parenchyma is ÅÎÁÉÑÅÓÇ = rifampin, ÌÓÁÖ
extremely unlikely to occur
o Immunologic diseases (eg, associated with
lupus, Goodpasture
syndrome) Ç ÉÁ ÄÉÁÌÅÓÇ ÍÅÖÑÉÔÉÄÁ
ÅÍÉÏÔÅ = ÅÎÁÍÈÇÌÁ +
o Acute transplant rejection ÁÉÌÁÔÏÕÑÉÁ
transforming growth factor beta
(TGFâ) Õ ÏÕËÇ ÅÃÊÁÔÁÓÔÁÓÇ
o Infections:
„h Bacterial (must be accompanied by ÓÙËÇÍÁÑÉÁÊÇÓ ÄÉÁÔÁÑÁ ÇÓ
= a major participant in = Fanconi syndrome :
obstruction or
fibrogenesis ÁÌÉÍÏÎÕÏÕÑÉÁ – ÃËÕÊÏÆÏÕÑÉÁ
reflux)
„h Viral (eg, cytomegalovirus [CMV], –ÍÅÖÑÏÓÙËÇÍÁÑÉÁÊÇ ÏÎÅÙÓ]
hantavirus, HIV,
favors accumulation of collagen
hepatitis B)
and noncollagen basement ÑÙÔÅÉÍÏÕÑÉÁ = Á ÏÕÓÉÁÆÅÉ
„h Fungal (eg, histoplasmosis)
membrane components ÅÉÍÁÉ Ç ÉÁ
„h Parasitic (eg, Leishmania, Toxoplasma)
by direct stimulation of production
and by
o ÏÕÑÉÍÁËÕÓÇ =
inhibiting matrix degradation o ÌÉÊÑÏÓÊÏ ÉÊÇ
enzymes such as collagenases ÁÉÌÁÔÏÕÑÉÁÓÔÅÉÑÁ ÕÏÕÑÉÁ
and metalloproteinases o ÌÅ / ÁÍÅÕ ÅÙÓÉÍÏÖÉËÁ
ÁÍ ÊÁÉ Ç ÊËÉÍÉÊÇ ÅÉÊÏÍÁ ÅÉÍÁÉ
÷ñïíéïò ìïñö : ÔÕ ÉÊÇ ÊÁÔÁ ÊÁÍÏÍÁ
ÄÉÁÃÍÙÓÇ ÔÉÈÅÔÁÉ ÌÏÍÏ ÌÅÔÁ
öáñìáêá nuclear factor kappa B (NF-êâ) Á Ï ÂÉÏØÉÁ
âáñåá ìåôáëëá
á ïöñáêôéêç ïõñï áèåéá =Activation of nuclear ÌÓÁÖ ÔÏÎÉÊÏÔÇÔÁ = ÂÁÑÅÉÁ
áíïóïëïãéêåò áèçóåéò transcription factors
íåï ëáóéá
ìåôáâïëéêåò áèçóåéò in injured kidney : o Antibiotics (eg, penicillins,
ãåíåôéêåò áèçóåéò cephalosporins, sulfa drugs,
Âáëêáíéêç åíäçìéêç íåöñï áèåéá release of proinflammatory quinolones)
Chinese herb/aristolochic acid nephropathy cytokines into the interstitium, o NSAIDs
appears to be a major o Diuretics (eg, thiazides,
mechanism of chronic furosemide)
tubulointerstitial inflammation o Allopurinol
accompanying proteinuric kidney o Phenytoin
diseases o Rifampin
Ç ÊÕÔÔÁÑÉÊÇ ÊÁÔÁÓÔÑÏÖÇ ÓÕÍÅ ÁÃÅÔÁÉ ÔÇÍ o Interferon alfa
ÁÑÏÕÓÉÁ ÁÍÔÉÃÏÍÙÍ ÓÅ ÔÏ ÉÊÏ Å É ÅÄÏ, o Proton pump inhibitors
ÄÉÇÈÇÓ ÌÅ ÊÕÔÔÁÑÁ ÖËÅÃÌÏÍÇÓ,
ÅÍÅÑÃÏ ÏÉÇÓÇ ÑÏÖËÅÃÌÏÍÏÄÙÍ ÊÁÉ 10-15% of Acute allergic interstitial
ÇÌÅÉÏÔÁÊÔÉÊÙÍ ÊÕÔÔÏÊÉÍÙÍ ÌÅ ÔÅËÉÊÇ ÅÊÂÁÓÇ all kidney diseases both in the United nephritis should not be
Ï ÅÉÁ ÅÉÔÅ ÑÏÍÉÏ ÍÅÖÑÉÔÉÄÁ States and around confused with the acute
the world vasomotor renal insufficiency
ÏÎÅÉÁ ÄÉÁÌÅÓÏÓ ÍÅÖÑÉÔÉÄÁ = ÓÙËÇÍÁÑÉÁÊÇ that can occur in patients with
ÊÁÔÁÓÔÑÏÖÇ / ÄÕÓËÅÉÔÏÕÑÃÉÁ ÌÅ / ÁÍÅÕ Mortality/Morbidity preexisting underperfusion of
ÍÅÖÑÉÊÇ ÁÍÅ ÁÑÊÅÉÁ ÁÍÅÎÁÑÔÇÔÁ Á Ï ÔÇÍ o Tubulointerstitial disease may the kidney.
ÅÊÔÁÓÇ ÔÇÓ ÓÙËÇÍÁÑÉÊÁÇÓ ÊÁÔÁÓÔÑÏÖÇÓ, progress to end-stage renal
disease. A unique feature of allergic
Ç ÍÅÖÑÉÊÇ ÄÕÓËÅÉÔÏÕÑÃÉÁ ÊÁÔÁ ÊÁÍÏÍÁ o An increased incidence of interstitial nephritis
ÂÅËÔÉÙÍÅÔÁÉ / ÁÍÁÓÔÑÅÖÅÔÁÉ, ÁÍÔÁÍÁÊËÙÍÔÁÓ uroepithelial cancers is found among caused by NSAIDs is that
ÔÇÍ ÁÍÁÃÃÅÍÇÔÉÊÇ ÉÊÁÍÏÔÇÔÁ ÔÙÍ patients with analgesic nephropathy, patients may present with
ÓÙËÇÍÁÑÉÙÍ ÌÅ ÁÍÅ ÁÖÇ ÂÁÓÉÊÇ aristolochic acid nephrotic
ÌÅÌÂÑÁÍÇ nephropathy, and Balkan endemic syndrome. In such patients,
nephropathy. massive proteinuria with
hypoalbuminemia and edema
are prese

2. Antibiotic-induced acute Analgesic nephropathy Lead nephropathy
tubulointerstitial nephritis
ôï ë ïí óõ÷íü áßôéï, á ü íåöñï Üèåéá + ïõñéê
áñèñßôéäá
óå íïóïêïìåéáêü áóèåí õ ü áãùã ãéá óõíäõáóìü :
ëïéìÿîåéò phenacetin, aspirin, and caffeine
phenacetin + acetaminophen áßäåò = åãêåöáëï Üèåéá +
åîÜíèçìá NSAIDs and acetaminophen ÍÁ äéêçí fanconi
åùóçíüöéëá ^^ óå ïñü êáé ï ñá
áéìáôïõñßá è ëåá 6çò - 7çò äåêáåôßáò Õ ÅÑÔÁÓÇ !
éá ñùôåéíïõñßá : <1 g/d
õ üíïéá óå äéáëëåß ïõóá ÄÉÁÃÍÙÓÇ = EDTA
âéïøßá õåëïíåöñßôéäá :
lead mobilization test
åíßïôå åùóéíüöéëá
åíßïôå ill-defined granulomas are present í êñùóç èçëÿí
áéìáôïõñßá ËÁÍÈÁÓÌÅÓ ÄÃÍ/ÓÅÉÓ
â èéï Üëãïò åíßïôå + á üöñáîç
ëïßìùîç
ïõñéê íåöñï Üèåéá
%% å áóâåóôÿóåéò èçëÿí õ åñôáóéê
íåöñïóêë ñùóç
rifampin
áíáéìßá + óôåßñá õïõñßá +
óå å áíá÷ïñ ãçóç ìåôá´á ï 1 äéáóôçìá = ñùôåúíïõñßá
óõó÷ ôéóç ìå äéÜìåóç íåöñéôéäá
Obstructive uropathy
åíßïôå : %% åî ëéîç óå ÍÁ
++ åëáöñ ò Üëõóïé áíåõ á üäåéîçò % óõó÷ ôéóç ìå ïõñïå éèçëéáêÜ o prostate disease,
ìõåëÿìáôïò åï ëÜóìáôá o stone disease,
o neoplasm, and
++ IgG circulating antirifampin êáé o retroperitoneal fibrosis
åíÜ ïèåóç óôç âáóéê ìåìâñÜíç
ìåôáî Üëëùí ñïêáëåß
ÁÍÅÕ ÅÙÓÉÍÏÖÉËÉÁÓ Lithium nephropathy äéÜìåóç óùëçíáñéáê íüóï
óôï 50 % = ñùôåúíïõñßá +
ÂÕÈÉÏ ÁËÃÏÓ + Õ ÅÑÔÁÓÇ + ÃÑÉ ÙÄÅÓ õ åñêáëéáéìßá, óùëçíáñéáê
ÓÕÍÄÑÏÌÏ + ÏÍÁ ÌÅ ÏËÉÃÏÕÑÉÁ äéáôáñá÷ óôï Ü ù : ïî ùóç
o polyuria,
o concentrating defect, TORCH infections
o down-regulation of aquaporin-2 Toxoplasmosis Other (syphilis)
Rubella Cytomegalovirus
(CMV) Herpes simplex virus
miscellaneous agents ó áíßùò ÷ñüíéïò ìïñö , ìåôÜ á ï (HSV)
å áíçëëåéì íá å éóüäéá ôïîéêüôçôáò
Hantavirus, CMV, and HIV are common á ï õøçë ò óõãêåíôñÿóåéò ïñï
= ïõñçôçñïêõóôéê íüóïò ìå
ó åéñáìáïóêë ñõíóç êáé
HIV : äéÜìåóç + ó åéñáìáôïíåöñßôéäá íåöñùóéêü ïõ èá äÿóåé
åóôéáê ôìçìáôéê óêë ñõíóç óôçí ñí ëéêï æù äéÜìåóç
íåöñßôéäá áêüìç êáé åáí ç
Cyclosporine- and
ÂÁÊÔÇÑÉÁ : ó Üíéá Üíåõ á üöñáîçò áëéíäñüìçóç äéïñèÿèçêå
tacrolimus-induced íùñßò
nephropathy
éóôï ëÜóìùóç - öõìáôßùóç : ÄÄ ñüêëçóç = chronic transplant nephropathy Superimposed infection and
pyelonephritis often
óå ìåôáìïó÷å óåéò complicate
áñ, íåöñüò, ìõïêÜñäéï obstruction
ü÷é óå ìõåëï , ìéêñüôåñç äüóç !
óå äéáëëåß ïõóåò
ïõñïëïéìÿîåéò ñïäéÜèåóç
Chronic tubulointerstitial nephritis óõó÷ ôéóç ìå áããåéïó ó áóç, ï ãéá ammonium
ìç÷áíéóìüò = äßêçí á üññéøçò magnesium phosphate
óõ÷íÜ ôõ÷áßï å ñçìá ìïó÷å ìáôïò ëßèïõò, öáõëïò ê êëïò
Üíåõ óõìôùìÜôùí
éá åùò óïâáñ õ åñôáóç
äéêçí óùëçíáñéêá ò ïî ùóçò = ^êñåáôéíßíç
äéêçí fanconi áíáì íïíôáé :
éá ñùôåéíïõñßá
õ ñôáóç + õ åñêáëéáéìßá
÷áñáêôçñéóôéêü = low molecular weight (eg,
immunoglobulin light chains, beta2 êõêëïó ïñßíç : + õ ïìáãíçóéáéìßá
microglobulin,
lysozyme, peptide hormones) èñïìâïôéê ìéêñïáããåéï Üèåéá
= âëÜâç óôï åãã ò óùëçíÜñéï
ôåêìçñßùóç
äéÜìåóç ßíùóç
óùëçíáñéáê áôñïößá
áããåéáê óêë ñõíóç
äé èçóç á ü ìïíï ñçíá

3. Balkan endemic nephropathy á åéêïíßóåéò
Atherosclerotic kidney disease
åñéâáëëïíôéêüò áñÜãùí õ ñç÷ïò
ïíïìáóßåò = ÷ùñßò õ åñôáóç õäñïí öñùóç
o Échemic nephropathy, óçìáíôéê áíáéìßá ëßèïé
o renovascular disease, and
o nephrosclerosis >40% ïõñïå éèçëéáêÜ íåï ëÜóìáôá óôï ê.ö ì ãåèïò äåí á ïêëåßåé
áíÿôåñï ïõñï ïéçôéêü ÁÉÍ, åíäå÷ïì íùò
áíáóôñ øéìç
elderly white males who smoke %% ÍÁ ôåëéêï óôáäßïõ ìéêñü ì ãåèïò = ìç
individuals with dyslipidemia and other áíáóôñ øéìç âëÜâç
atherosclerotic phenomena
õ ñç÷ïò + KUB ëÜêá
Chinese herb åñé ÷ïíôá aristolochic acid ÄÄ óêéåñÿí / äéáöáíÿí ëßèùí
Often, these patients have hypertension, not êáé ïõ ÷ñçóéìï ïéï íôáé ãéá á ÿëåéá
necessarily severe, with elevated serum âÜñïõò
creatinine and urea nitrogen and proteinuria, CT
1-2 g/d ñïïäåõôéê äéÜìåóç óùëçíáñéêá áíáì íïíôáé å áóâåóôÿóåéò
íåöñßôéäá êáé äéÜìåóç éíùóç óôï õåëïêáëõêéêü
= ïñåßá âñáä ôåñç á ï ïôé óå íåöñùóéêü
ë.÷ ó ä - íåöñï Üèåéá ÃÜëéï
áñíçôéêü = äåí á ïêëåßåé ôç
íüóï
äéÜãíùóç Differential Diagnoses èåôéêï = ìç åéäéêü, áí
Acute Renal Failure õ Üñ÷åé õ üíïéá,
êëéíéê
Glomerulonephritis, Acute å áëçèå åé
ôåêìçñßùóç á åéêïíéóôéê á ïêáë ôïõóá
Urinary Tract Obstruction
áèçñïóêë ñùóç ôùí íåöñéêÿí áñôçñéù´í
äåí á éôåßôáé âéïøßá óõí èùò
Other Problems to Be Considered
Radiation nephritis
äåí õ Üñ÷åé åéäéê áíôéìåôÿ éóç, áãùã Toxic nephropathies
íáíôé õ ñôáóçò, êáé áíôéëé éäáéìéê
ëïé ò åîåôÜóåéò
Laboratory Studies EDTA lead mobilization test
Cholesterol microembolic disease and ç áñïõóßá ìïë âäïõ óôï
åùóéíïöéëßá :
nephropathy ç áñïõóßá ôçò âïçèÜ, áëëá´äåí åéßíáé áßìá åßíáé ÷ñ óéìç óå ïîåßá
åéäéê ìüíï íüóï
áõèüñìçôç á ïõóéÜæåé óå ÁÉÍ = Acute
õ ü áãùã ìå áíôé çêôéêÜ tubulointerstitial nephritis in children
á ïõóéÜæåé óå ÌÓÁÖ ôïîéêüôçôá ïéïôéêüò ñïóéïñéóìüò
ìåôÜ á ü äéáãíùóôéêï ò áããåéáêï ò ñùôåúíïõñßáò
êáèåôçñéáóìï ò
÷áçëïõ ìïñéáêï âáñïõò
á ïóôáèñï ïßçóç ôïõ áèçñÿìáôïò êáé êáé åëáöñ ò Üëõóïé
Blood chemistry:
á ïöñÜîåéò á ï ìéêñï ìâïëá íåöñéêÿí
ôñé÷ïåéäÿí á ü âåëïíïåéäåßò êñõóôÜëëïõò = âëÜâç óôï Ü ù
÷áìçëá äéôôáíèñáêéêÜ = ïîåßäùóç
÷áìçëü êÜëéï = âëÜâç óôï Ü ù
áìöéâëçóôñïåéä ò : Hollenhorst plaques ÷ñïíéïó ÁÉÍ
õøçëü êÜëéï + ÷áìçëÜ äéôôáíèñáêéêÜ =
ÊÍÓ âáëêáíéê íåöñßôéäá
óùëçíáñéáê ïî ùóç ôõ ïó 4 [ ÌÓÁÖ,
Üêñá : livedo reticularis êÜäìéï
ìüëõâäïò]
åíßïôå óõóôçìáôéê íüóïò
^^ ESR
ïõñéíÜëõóç :
õñ ôéï
÷áìçëü óõì ë ñùìá
áéìáôïõñßá
ëåõêïêõôôÜñùóç
ñùôåúíïõñßá
åùóéíïöéëßá
õïõñßá ìå / áíåõ âáêô ñéá
ëåõêïêõôôáñéêïß ê ëéíäñïé
äåí õ Üñ÷åé èåñá åßá åéäéê
ìéêñïóêï éê
ê ëéíäñïé
ëåõêïêõôôáñéêïß ê ëéíäñïé
åùóéíüöéëá
Metabolic disorders and êñ óôáëëïé
nephropathy
If allergic interstitial nephritis is suspected,
õ åñáóâåóôéáéìßá, áêüìç êáé ç áñïäéê send a cytospin specimen to determine if
êõóôéê ßíùóç eosinophils are in the urine
chronic potassium depletion
õ ïëåé ÿìåíç óõì êíùóç, ïëõïõñßá
áíáì íùíôáé íåöñéê ò å áóâåóôÿóåéò, ç
ëéèßáóç óõíéóôÜ ä óêïëç ôç äéá÷åßñçóç

4. å é ëüêåò
äéá÷åßñçóç
õ ñôáóç
äéáêï ôïîéêï áñÜãïíôá
çëåêôñïëõôéê ò äéáôáñá÷ ò
óå ìç âåëôßùóç åíôüó çìåñùí :
Prednisone 0.5-2 mg/kg/d PO, taper as ÍÁ ïõ á áéôåß äéë çóç
condition improves; single am dose
safer for long-term use, but divided doses
have greater antiinflammatory
effect
Modifies the body's immune response to
diverse stimuli
ñüãíùóç
o May decrease inflammation by reversing
increased capillary permeability and
o suppressing PMN [= PML = Allergic interstitial nephritis:
polymorphonuclear leukocytes ] activity.
o Stabilizes lysosomal membranes and êáôÜ êáíüíá õ ï÷ùñåß
o suppresses lymphocytes and antibody
production
Cholesterol microembolic kidney
disease:
monitor for hypokalemia with
coadministration of diuretics äåí õ Üñ÷åé ë ñçò âåëôßùóç, ßáóç
Chelating agents
Chronic tubulointerstitial
Succimer (Chemet) nephritides:
Metal chelator, analog of dimercaprol.
êáôáë ãåé óå ÍÁ áëëÜ åßíáé
Used in lead poisoning. ëéãüôåñï å éèåôéê á ü ôéò
ó åéñáìáôïíåöñßôéäåò
Particularly useful in children with lead
blood levels >45 mcg/dL.
Edetate calcium disodium (Calcium
Disodium Versenate)
For lead chelation. Only the calcium
disodium preparation
should be used.