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Tubulointerstitial
nephritis
Dr F. MOEINZADEH
Case 1
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A 34 y/o female is evaluated for Cr rising.
She has low back pain from 15days ago and
consume Iboprofen tab 4times /day.
Nausea +, no vomiting, no oliguria
PH.Ex: T=37.1°C RR=18/min
PR= 85/min
Other finding is unremarkable
Case 2
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A 74 years old man with low back pain and anemia
referred to nephrology clinic due to Cr rising.
Lab data: Cr= 3.2 mg/dL Ca= 11.7mg/dL
Alb= 3.8 g/dL
Hb= 9.3g/dL MCV=85fl
PLT=143000/mm3
Kidney sonography: RT kidney= 120mm LT
kidney= 115mm and some calcifications in both
kidneys.
Tubulointerstitial Nephritis
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A group of clinical
disorders that
affect principally
the renal tubules
and interstitium
with relative
sparing of
glomeruli and
renal vasculature
Classification:
1. AIN: acute IN
2. CIN: chronic IN
Acute Interstitial Nephritis
AIN is a clinicopathologic syndrome
of:
 ARF
 Associated
with interstitial edema and
cellular infiltrate
Acute Interstitial Nephritis
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Etiology
Idiopathic
Secondary
Secondary Causes of ATIN
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Drugs:
Antibiotics: Penicillins, Cephalosporins, Sulfa drugs,
Ciprofloxacin, Acyclovir
NSAIDS
Diuretics: Thiazides, Furosemide, Triamterene
Others: Cimetidine, Omeprazole, Phenytoin, Allopurinol
 Systemic infection: Legionnaires disease, Leptospirosis,
Streptococcal infection, CMV infection
 Primary kidney infections: Acute bacterial
pyelonephritis.
 Autoimmune disorders: Sarcoidosis, Sjogrene syndrome
Pathophysiology – drug induced AIN
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Drug-induced AIN is secondary to
immune reaction
 AIN
occurs only in a small percentage
of individuals taking the drug
 AIN is not dose-dependent
 Association with extrarenal
manifestations of hypersensitivity
 Recurrencence after re-exposure to
the drug
TYPICAL CLINICAL MANIFESTATION OF
ACUTE INTERSTITIAL NEPHRITIS
History of drug hypersensitivity or recent
infection and taking antibiotics
 Sudden onset of fever lasting several days to
weeks
 Variable degrees of hypertension
 Triad: fever, rash, eosinophilia: typical but
unusual presentation
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Flank pain due to capsule distention
 Most presentation: any of this features
 Hypertension , edema is uncommon in AIN
 A particularly severe and rapid-onset AIN may
occur upon reintroduction of rifampin after a
drug-free period
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Laboratory Findings in AIN
Acute rise in plasma cr
 Eosinophilia
 Sterile pyuria
 Positive Hansel stain (>1% total WBCs are
eos): rarely
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Laboratory Findings in AIN
Active urine sediment with WBC, RBC, and
WBC casts
 Normal or mildly increased protein excretion
(usually no more than 1g/day)
 Renal tubular acidosis
 Rise in creatinine with FENa >1.0; no expected
acute tubular necrosis or glomerulonephritis
 Kidney size normal or increased
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Eosinophiluria
Other conditions associated with
Eosinophiluria
Prostatitis
 Upper & lower UTI
 Bladder Cancer
 Renal Atheroembolic disease
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Diagnostic Studies
CBC
 Urinalysis
 Hansel stain
 Renal ultrasound
 Gallium scan
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Renal biopsy
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Gold standard is renal biopsy. Indications are:
 Uncertainty of diagnosis
 Advanced RF
 Lack of spontaneous recovery after cessation
of offending drug
 If immunosupressive therapy is considered
 Renal biopsy is generally not required for
diagnosis but reveals extensive interstitial and
tubular infiltration of leukocytes, including
eosinophils.
Algorithm for the treatment of allergic
and other immune-mediated AIN
Prognosis
Most cases of AIN resolve completely after
offending factor has been removed.
 The longer the patient remains in renal
failure, the less likely it is that complete
recovery of renal function will occur.
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Chronic interstitial nephritis
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A clinicopathologic entity defined as slowly
progressive renal insufficiency due to
tubular cell atrophy and progressive
interstitial fibrosis caused by a chronic
interstitial mononuclear cell infiltrate.
CTIN is responsible for 15-30% of all cases of
ESRD.
Conditions assiciated with CTIN
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Hereditary: ADPKD, Alport
Metabolic disturbances: hypercalcemia,
hyperoxaluria, hyperuricemia, hypokalemia,
cystinosis
Drugs & toxins: NSAIDS, lead, lithium, cisplatin,
cyclosporine, tacrolimus, Chinese herbs.
Immune mediated: Wegener granulomatosis,
sjogrene, SLE, sarcoidosis, vasculitis
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Hematologic & malignancies: MM, Sickle cell
anemia, lymphoma
Infections: chronic pyelonephritis,
xanthogranulomatous pyelonephritis
Obstruction: tumors, stones, bladder outlet
obstruction, vesicoureteral reflux.
Others: radiation nephritis, hypertensive
atherosclerosis, renal ischemic disease
Clinical manifestations
Usually asymptomatic until develop CKD
eg: malaise, nausea, nocturia, sleep
disturbances
 Is sometimes found incidentally on routine
Lab work: decreased GFR (Cr rise), U/A:
PU. Microscopic hematuria, pyuria.
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Clinical findings that suggest chronic TIN
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Hyperchloremic metabolic acidosis
Hyperkalemia (out of proportion of RF)
Reduced maximal urinary concentrating ability
(polyuria, nocturia)
Partial or complete fanconi syndrome(
phosphaturia, bicarbonaturia, Aauria, uricosuria,
glycosuria)
Modest proteinuria (<2 gr/day)
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RTA II( proximal RTA) :
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lead poising
MM
RTA I( Distal): chronic urinary obstruction
Polyuria: analgesic nephropathy, sickle cell disease,
PKD.
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Etiologies
Metabolic disturbances
 Analgesic nephropathy
 Lead nephropathy
 Chinese herb nephropathy
 Sarcoidosis
 MM
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Metabolic disturbances
Hyperclcemia: can lead to nephrocalcinosis (
deposition around tubules and collecting ducts)
 Acute hyperphosphatemia, sodium phosphate
solution lead to nephrocacinosis ( incompletely
reversible after hypercalcemia resolve)
 Prolong hyperuricemia
 Hyperoxaluria (in jojenoileal bypass)
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Analgesic nephropathy
Medication contain: aspirin, acetaminophen,
phenacetin, caffeine, codeine.
 Acetaminophen: 1. is concentrate in the
papillary tips 2. its reactive metabolites can
injure cells in the renal papilla, papillary
necrosis.
 This effect can exagerate with concomitant
NSAIDs use.
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Analgesic nephropathy
Usually occur in young women who had comorbidities of emotional stress,
neuropsychiatric problem, GI disturbances.
 Plain CT: papillary calcification, abnormal
renal cortex contour.
 Tx: cessation of drug
 BUT: progression of renal function loss is usually
slowed or even arrested with drug
discontinuation.
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Lead nephropathy
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Lead taken up by PCT that cause aminoaciduria,
glycosuria, CIN.
Triad: HTN, gout (saturnine gout) and chronic renal
insufficiency.
Dx: elevated 24h urinary excretion of lead after
administration of 2 , 1g doses of EDTA.
Tx: chelation therapy with EDTA that arrest or even
reverse the CKD.
Chinese herb nephropathy
Silent renal insufficiency
 Fanconi syndrome or fatigue from anemia
 Rapidly progressive CIN with accelerated
interstitial fibrosis, lead to ESRD.
 Tx: cessation of herbs
 Note: urothelia malignancy monitoring
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Sarcoidosis
The most common cause of renal dysfunction:
hypercalcemia.
 Cause noncaseating granolomatous interstitial
nephritis.
 RTA II
 CIN respond to corticosteroid therapy: loss of
granolomatous & lymphocytic infiltrate.
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Multiple myeloma
Induce acute & chronic renal dysfunction.
 Tubulointerstitial pathology:
light chain cast nephropathy: most
common complication.
hypercalcemia with nephrocalcinosis
hyperuricemia
amyloid deposition
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MM
light chain cast nephropathy: cast clogging the
tubule initiate a multinucleated giant cell
inflammatory reaction.
 Tx: chemotherapy to reduce excess production,
volume repletion and alkalization of the urine.
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Urinary tract obstruction
Acute & chronic urinary tract obstruction are
associated with a mononuclear cell infiltrate.
 Obstruction cause: CIN
Impaired excretion of H+& K
vasopressin- resistant
concentrating defect.
 Tx: relief of the obstruction
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Radiation nephritis
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In radiation more than: 2300cGy
Acute and severe injury within 1 year of radiation:
HTN, anemia, edema
Insidious chronic form: mild renal insufficiency, HTN,
mild proteinuria.
Pathogenesis: injury to the vascular endothelium,
vascular occlusion, tubular atrophy, interstitial
fibrosis.
Hypertensive arterionephrosclerosis
Arteriopathy in the afferent arterioles leading
to interstitial & glomerular changes related to
ischemia.
 Prominent cause of the loss of renal function:
Tubular atrophy & interstitial fibrosis.
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