Interstitial Renal Disease

S. Kadiri
Introduction

Definition
Classification
Causes
Clinical features
Investigations
Treatment
Definition

Interstitium
Unilateral or bilateral
Worldwide
Age, gender, race issues
About 15% CKD, maybe higher
Issue of hypertensive nephrosclerosis
Acute interstitial nephritis
Immunologic

Hypersensitivity

Infections

Transplant rejection

Acute tubular necrosis
Immunologic
Perhaps commonest

SLE

Goodpastures syndrome

Wegeners granulomatosis
Drugs
Antibiotics
-penicillin, sulfa, quinolones, rifampin, cephals
NSAIDS
Diuretics
-thiazides, frusemide
Allopurinol
Phenytoin

Infections
Bacterial
with obstruction, reflux

Viral CMV, HIV, Hep-B

Fungal

Parasitic
Clinical features - AIN
Usually within days
Rash
Fever
Usually mild proteinuria
Acute renal failure
Eosinophilia
Eosinophiluria
Elevated IgE
Chronic interstitial nephritis
CIN - Causes
Immunologic diseases
Drugs
Obstructive uropathy, reflux disease
Heavy metals
Atherosclerotic renal disease
Neoplasia
Metabolic diseases
Balkan nephropathy
Aristolochic acid nephropathy
Genetic causes
Immunologic diseases
SLE, Prim glomerulopathies, Sjogrens,
sarcoidosis

Vasculitis, ANCA + vasculitis, Wegeners

Chronic transplant nephropathy
Drugs
Analgesics

Lithium

Cyclosporine

tacrolimus
Heavy metals
Lead

Cadmium

mercury
Neoplasia
Myeloma

Lymphomas

Leukaemias

Metabolic Disorders
Gouty nephropathy
Hypercalcaemia
Hypokalaemia
Hyperoxaluria
Cystinosis
Fabrys disease
Hereditary disorders
Autosomal dominant interstitial kidney disease
(medullary cystic kidney disease,
uromodulin-associated kidney disease,
renin-associated hereditary interstitial
kidney disease)
Medullary sponge kidney
ADPKD
Hereditary nephritis (Alports syndrome)


Pathogenesis
Injury to renal cells
New local antigens
Inflammatory cells infiltration
Activation of proinflammatory and
chemoattractant cytokines

Renal tubular dysfunction
Role of basement membrane

Fibrogenesis
TGF-beta
-Stimulates production of collagen and non-
collagen basement membrane components
-Inhibits collagenases and metalloproteinases

Activation of nuclear transcription factors
such as nuclear factor kappa B
- release of proinflammatory cytokines



Clinical features - CIN

Insidious
Hypertension
Renal tubular acidosis
Fanconi syndrome
Mild proteinuria
Investigations
Urinalysis
Proteinuria
albuminuria.
beta-2 microglobulin, RBP,
N-acetylglucosaminidase
Haematuria
Leucocyturia
Eosinophiluria
White cell casts
Blood count
Eosinophilia

Eosinophiluria

Eosinophilia absent in NSAID induced AIN

Elevated ESR
Blood chemistry
Acidosis

Low phosphate, potassium in PT disorders

Elevated K and acidosis in type-4 RTA

Creatinine and urea
Imaging
Plain film, Ultrasound, CT scan


Renal size, echogenicity
Calyceal dilatation
Stones
Calcifications
Other tests
EDTA Lead mobilization tests
X-ray fluorescence



Renal biopsy
Treatment

ACUTE
Cessation of offending agent
Antimicrobial therapy
Steroid therapy
1mg/Kg for 4-6 weeks

CHRONIC
Supportive measures




Specific forms
NSAID induced AIN
Commoner in elderly

Allergic

Eosinophilia uncommon

Nephrotic syndrome common

Minimal change disease + interstitial nephritis
Antibiotic induced AIN
Within days to weeks
Rash
Eosinophilia, eosinophiluria
(not with rifampin)
Sterile pyuria
Haematuria
Proteinuria usually < 1g
Analgesic nephropathy
Most common cause of CIN worldwide
Long term ingestion
Phenacetin, NSAIDs, Phenacetin + NSAID
2-3 Kg over years
Commoner F>M, 6
th
-7
th
decades
Haematuria, flank pain, infection
Mild proteinuria, sterile pyuria, reduced GFR
Papillary tip microcalcifications
Treatment supportive
Increased incidence of uroepithelial tumours
Lead nephropathy
Long biologic half life
CIN in 3
rd
-4
th
decade
Paints, batteries, leaded fuel welding, smelting
Hypertension almost always present
Hyperuricaemia
Confusion with hypertensive nephrosclerosis
and gouty nephropathy
Removal from lead
Chelation more useful in acute poisoning

Ischaemic nephropathy
Elderly, smoking, dyslipidaemia
Hypertension, proteinuria 1-2 g,
Elevated se-creatinine
Duplex scanning, DSA, MRI
Tubular atrophy, fibrosis, arteriolar sclerosis
Little cellular infiltration
Treatment supportive
Aristolochic acid Nephropathy
Aristolochic acid in Chinese slimming herbs
Banned product
Dose-response relationship
Progressive interstitial fibrosis
Likely cause of Balkan nephropathy
(wheat flour contamination by seeds of
Aristolochia clematitis)
Uro-epithelial cancer
Cholesterol microembolic disease
Destabilisation of plaques
Lodging of needle shaped cholesterol crystals
Kidneys, also skin, brain, retina, extremities
May be fever, leucocytosis, eosinophilia,
raised ESR, hypocomplementaemia
ARF with residual impairment
Needle shaped clefts in small and medium
arteries
Mononuclear cellular infiltration
No effective treatment